About Bolder Science

Our mission is to provide healthcare professionals with unbiased clinical research information, easily.

Currently, you can access the following clinical trials being conducted worldwide:

378040 studies
in
220 countries
Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 06/15/2021.
This website is for US healthcare professionals

Log In to Bolder Science

or

Don't have an account? Sign Up

Please enter your email address.

You will receive a link to create a new password via email.

Log In

Create an Account

or
(optional) ?

Welcome, !

Please complete the following 4 questions to ensure you receive the information that best suits your needs.

Clinical Trials of Interest

When I’m looking for information on clinical trials, I usually am interested in...

finding clinical trials in which to enroll my patients

Rarely Often

finding newly launched clinical trials (for all phases)

Rarely Often

updates on status changes for clinical trials

Rarely Often

pipeline molecules

Rarely Often

Drug Interventions

Enter up to 3 drug interventions you are currently interested in:

Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 06/15/2021.

A Study to Evaluate Drug-Drug Interaction of TAK-788 With Itraconazole and Rifampin in Healthy Adult Participants

Clinicaltrials.gov identifier NCT03928327

Recruitment Status Completed

First Posted April 26, 2019

Result First Posted August 21, 2020

Last update posted August 21, 2020

Study Description

Brief summary:

The purpose of this study is to characterize the effect of itraconazole (Part 1) and rifampin (Part 2) on the single-dose pharmacokinetics (PK) of TAK-788 and its active metabolites (AP32960 and AP32914) in healthy adult participants.

  • Condition or Disease:Healthy Volunteers
  • Intervention/Treatment: Drug: TAK-788
    Drug: Itraconazole
    Drug: Rifampin
  • Phase: Phase 1
Detailed Description

The drug being tested in this study is called TAK-788 (Mobocertinib). The study assessed the drug-drug interaction of TAK-788 with either a strong cytochrome P-450 (CYP)3A inhibitor, itraconazole (Part 1) or with a strong CYP3A inducer, rifampin (Part 2) in healthy adult participants. The study enrolled 24 healthy participants. The study was designed to consist of 2 parts: Part 1- TAK-788 assessment with itraconazole Part 2- TAK-788 assessment with rifampin. Part 1 had 2 cohorts: Part 1: Participants (n = 12) received a single oral dose of 20 mg capsule of TAK-788 on Day 1 of Period 1 followed by 200 mg itraconazole oral solution once daily (QD) in Period 2 on Days 1 to Day 14 and a single oral dose of TAK-788 20 mg capsule were coadmistered on Day 5 of Period 2. In Part 2 participants (n = 12) received a single oral 160 mg dose of TAK-788 capsules in Period 1 of Day 1 followed by 600 mg capsules of rifampin QD in Period 2 Days 1 to Day 13 and a single dose of 160 mg TAK-788 capsules was coadministered on Day 7 of Period 1. There was a washout period of 7 days between the dose of TAK-788 on Period 1 and the first dose of rifampin in Period 2. This single-center trial was conducted in the United States. The overall time to participate in this study was approximately 120 days (including screening period). Participants were contacted by telephone 30 days after the last dose of study drug for a follow-up assessment.

Study Design
  • Study Type: Interventional
  • Actual Enrollment: 24 participants
  • Allocation: Non-Randomized
  • Intervention Model: Sequential Assignment
  • Masking: None (Open Label) ()
  • Primary Purpose: Other
  • Official Title: A Phase 1 Study of Oral TAK-788 to Evaluate the Drug-Drug Interaction With Itraconazole and Rifampin in Healthy Adult Subjects
  • Actual Study Start Date: May 2019
  • Actual Primary Completion Date: August 2019
  • Actual Study Completion Date: August 2019
Arms and interventions
Arm Intervention/treatment
Experimental: Part 1, Treatment Sequence AB
TAK-788 20 mg, capsule, at Hour 0 on Day 1 followed by an overnight fast (Treatment A). Following Treatment A, participants received itraconazole 200 mg solution, orally, once daily (QD) on Days 1 to Day 14 and a single oral dose of TAK-788 20 mg capsule was coadministered on Day 5 (Treatment B). There was a washout period of 7 days between the two treatments.
Drug: TAK-788
TAK-788 Capsules

Drug: Itraconazole
Itraconazole Oral solution
Experimental: Part 2, Treatment Sequence CD
TAK-788 160 mg, orally, at Hour 0 on Day 1 following an overnight fast (Treatment C). Following Treatment C, participants received rifampin 600 mg as capsules, orally, once daily (QD) on Days 1 to 13 and TAK-788 160 mg as capsules, orally was coadministered on Day 7 (Treatment D). There was a washout period of 7 days between the two treatments.
Drug: TAK-788
TAK-788 Capsules

Drug: Rifampin
Rifampin Capsules
Outcome Measures
  • Primary Outcome Measures: 1. Treatment B vs Treatment A (Part 1), Combined Molar Exposure for Cmax: Maximum Observed Plasma Concentration of TAK-788, AP32960, and AP32914 [ Time Frame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose ]
    The combined molar exposure Cmax for TAK-788 and its metabolites AP32960 and AP3914 value was calculated as the sum of each molar Cmax which was multiplied by 1000 and divided by molecular weight of each analyte, TAK-788, AP32960, and AP32914 respectively. The combined molar exposure was presented in nanomolar.
  • 2. Treatment D Vs Treatment C (Part 2), Combined Molar Exposure for Cmax: Maximum Observed Plasma Concentration of TAK-788, AP32960, and AP32914 [ Time Frame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose ]
    The combined molar exposure Cmax for TAK-788 and its metabolites AP32960 and AP3914 value was calculated as the sum of each molar Cmax which was multiplied by 1000 and divided by molecular weight of each analyte, TAK-788, AP32960, and AP32914 respectively. The combined molar exposure was presented in nanomolar.
  • 3. Treatment B Vs Treatment A (Part 1), Combined Molar Exposure for AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity, Calculated Using the Observed Value of the Last Quantifiable Concentration of TAK-788, AP32960, and AP32914 [ Time Frame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose ]
    The combined molar exposure AUC∞ for TAK-788 and its metabolites AP32960 and AP3914 value was calculated as the sum of each molar AUC∞ which was multiplied by 1000 and divided by molecular weight of each analyte, TAK-788, AP32960, and AP32914 respectively. The combined molar exposure was presented in hour*nanomolar.
  • 4. Treatment D Vs Treatment C (Part 2), Combined Molar Exposure for AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity, Calculated Using the Observed Value of the Last Quantifiable Concentration of TAK-788, AP32960, and AP32914 [ Time Frame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose ]
    The combined molar exposure AUC∞ for TAK-788 and its metabolites AP32960 and AP3914 value was calculated as the sum of each molar AUC∞ which was multiplied by 1000 and divided by molecular weight of each analyte, TAK-788, AP32960, and AP32914 respectively. The combined molar exposure was presented in hour*nanomolar.
  • 5. Tmax - Time to Reach the Maximum Plasma Concentration (Cmax) of TAK-788 [ Time Frame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose ]
  • 6. Tmax - Time to Reach the Maximum Plasma Concentration (Cmax) of AP32960 [ Time Frame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose ]
  • 7. Tmax - Time to Reach the Maximum Plasma Concentration (Cmax) of AP32914 [ Time Frame: Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose ]
Eligibility Criteria
  • Ages Eligible for Study: 18 to 55 Years (Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers: Yes
Criteria

Key Inclusion Criteria:

1. Continuous non smoker who has not used nicotine containing products for at least 3
months prior to the first dose and throughout the study based on participant
self-reporting.

2. Medically healthy with no clinically significant medical history, physical
examination, laboratory profiles, vital signs, or electrocardiograms (ECGs), as deemed
by the Investigator or designee. Has liver function tests (LFTs) including alanine
aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP),
and total bilirubin within the upper limit of normal at screening and at first
check-in.

3. Normal baseline spirometry for forced vital capacity (FVC) and forced expiratory
volume (FEV1)/FVC within 7 days prior to the first dosing based on the following
normal FVC and FEV1/FVC range: a. 20 - 39 years of age: ≥ 80% and b. 40 - 55 years of
age: ≥ 75%

4. Body mass index (BMI) ≥18.0 and ≤32.0 kg/m^2, at screening.

Key Exclusion Criteria:

1. History or presence of alcoholism or drug abuse within the past 2 years prior to the
first dosing.

2. History or presence of hypersensitivity or idiosyncratic reaction to the study drugs
or related compounds.

3. Presence of an acute lung infection, within 3 months of screening.

4. History or presence of any previous lung disease.

5. Part 1 only: History or presence of any of the following, deemed clinically
significant by the PI or designee, and as confirmed by the Sponsor:

- Ventricular dysfunction or risk factors for Torsades de Pointes (e.g., heart
failure, cardiomyopathy, family history of Long QT Syndrome);

- Uncorrected hypokalemia (potassium levels <3.7) and/or hypomagnesemia (magnesium levels 460 msec (males) or >470 msec (females) or ECG findings are deemed
abnormal with clinical significance by the Investigator or designee at screening.

10. Estimated creatinine clearance <90 mL/min at screening 11. Unable to refrain from or anticipates the use of: - Any drug, including prescription and non-prescription medications, herbal remedies, or vitamin supplements within 14 days prior to the first dosing and throughout the study. Medication listed as part of acceptable birth control methods will be allowed. Thyroid hormone replacement medication may be permitted if the subject has been on the same stable dose for the immediate 3 months prior to the first dosing. Acetaminophen (up to 2 g per 24 hour period) may be permitted during the study, only after initial dosing. - Any drugs known to be inhibitors or inducers of CYP3A enzymes and/or P-gp, including St. John's Wort, within 28 days prior to the first dosing and throughout the study. Appropriate sources (e.g., Flockhart Table™) will be consulted to confirm lack of pharmacokinetic (PK)/pharmacodynamics interaction with study drugs.

Contacts and Locations
Contacts
Locations

United States, Arizona
Celerion
Tempe

Sponsors and Collaborators

Millennium Pharmaceuticals, Inc.

Investigators

Study Director: Medical Director Millennium Pharmaceuticals, Inc.

More Information
  • Responsible Party: Millennium Pharmaceuticals, Inc.
  • ClinicalTrials.gov Identifier: NCT03928327 History of Changes
  • Other Study ID Numbers: TAK-788-1006
  • First Posted: April 26, 2019 Key Record Dates
  • Last Update Posted: August 21, 2020
  • Last Verified: August 2020
  • Individual Participant
    Data (IPD) Sharing
    Statement:
  • Plan to Share IPD: Yes
  • Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.
  • Studies a U.S. FDA-regulated Drug Product: Yes
  • Studies a U.S. FDA-regulated Device Product: No
  • Keywords provided by Millennium Pharmaceuticals, Inc.: Drug Therapy
  • Study Type: Interventional
  • Study Design: Allocation: Non-Randomized;Intervention Model: Sequential Assignment;Masking: None (Open Label);Primary Purpose: Other
  • Condition: Healthy Volunteers
  • Interventions : Drug: TAK-788
    Drug: Itraconazole
    Drug: Rifampin
  • Enrollment: 24
Participant flow
Recruitment Details Participants took part in the study in the United States from 02 May 2019 to 16 August 2019.
Pre-assignment Details Healthy participants were enrolled in this 2-period study to receive: TAK-788 20 mg (Treatment A) along with itraconazole 200 mg (Treatment B) and TAK-788 160 mg (Treatment C) with rifampin 600 mg (Treatment D) in sequential manner to evaluate drug-drug interaction.
Arm/Group title Part 2, Treatment Sequence CD Part 1, Treatment Sequence AB
Arm/Group Description TAK-788 160 mg, orally, at Hour 0 on Day 1 following an overnight fast (Treatment C). Following Treatment C, participants received rifampin 600 mg as capsules, orally, once daily (QD) on Days 1 to 13 and TAK-788 160 mg as capsules, orally was coadministered on Day 7 (Treatment D). There was a washout period of 7 days between the two treatments. TAK-788 20 mg, capsule, at Hour 0 on Day 1 followed by an overnight fast (Treatment A). Following Treatment A, participants received itraconazole 200 mg solution, orally, once daily (QD) on Days 1 to Day 14 and a single oral dose of TAK-788 20 mg capsule was coadministered on Day 5 (Treatment B). There was a washout period of 7 days between the two treatments.
Period Title: Period 2
Started 12 12
Completed 12 12
Not Completed 0 0
Reason Not Completed
Period Title: Washout Period
Period Title: Period 1
Baseline Characteristics
Arm/Group title TotalPart 2, Treatment Sequence CDPart 1, Treatment Sequence AB
Arm/Group Description Total of all reporting groupsTAK-788 160 mg, orally, at Hour 0 on Day 1 following an overnight fast (Treatment C). Following Treatment C, participants received rifampin 600 mg as capsules, orally, once daily (QD) on Days 1 to 13 and TAK-788 160 mg as capsules, orally was coadministered on Day 7 (Treatment D). There was a washout period of 7 days between the two treatments.TAK-788 20 mg, capsule, at Hour 0 on Day 1 followed by an overnight fast (Treatment A). Following Treatment A, participants received itraconazole 200 mg solution, orally, once daily (QD) on Days 1 to Day 14 and a single oral dose of TAK-788 20 mg capsule was coadministered on Day 5 (Treatment B). There was a washout period of 7 days between the two treatments.
Overall Number of Baseline Participants 241212
Baseline Analysis Population Description Safety Set included participants who received at least one dose of a study drug.
Region of Enrollment Measure Type: Count of Participants Unit of Measure: Participants Number Analyzed 24 Participants12 Participants12 Participants
Outcome Measures
1. PrimaryOutcome
Title Tmax - Time to Reach the Maximum Plasma Concentration (Cmax) of AP32914
Description
Time Frame Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose
Outcome Measure Data
Analysis Population Description
PK Set included participants who complied sufficiently with the protocol and display an evaluable PK profile. Overall number analyzed is the number of participants with data available for analyses.
 
Arm/Group title Part 2, Treatment DPart 2, Treatment CPart 1, Treatment BPart 1, Treatment A
Arm/Group Description Following Treatment C, participants received rifampin 600 mg as capsules, orally, once daily (QD) on Days 1 to 13 and TAK-788 160 mg as capsules, orally was coadministered on Day 7 in Period 2.TAK-788 160 mg, orally, at Hour 0 on Day 1 following an overnight fast in Period 1.Following Treatment A, participants received itraconazole 200 mg solution, orally, once daily (QD) on Days 1 to Day 14 and a single oral dose of TAK-788 20 mg capsule was coadministered on Day 5 in Period 2.TAK-788 20 mg, capsule, at Hour 0 on Day 1 followed by an overnight fast in Period 1.
Overall Number of Participants Analyzed 81289
Measure Type: Median (Full Range)
Unit of Measure: hr
4.00
(1.03 to 119.92)
6.00
(4.0 to 6.01)
8.00
(6.0 to 12.0)
6.00
(2.0 to 8.0)
2. PrimaryOutcome
Title Tmax - Time to Reach the Maximum Plasma Concentration (Cmax) of AP32960
Description
Time Frame Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose
Outcome Measure Data
Analysis Population Description
PK Set included participants who complied sufficiently with the protocol and display an evaluable PK profile.
 
Arm/Group title Part 2, Treatment DPart 2, Treatment CPart 1, Treatment BPart 1, Treatment A
Arm/Group Description Following Treatment C, participants received rifampin 600 mg as capsules, orally, once daily (QD) on Days 1 to 13 and TAK-788 160 mg as capsules, orally was coadministered on Day 7 in Period 2.TAK-788 160 mg, orally, at Hour 0 on Day 1 following an overnight fast in Period 1.Following Treatment A, participants received itraconazole 200 mg solution, orally, once daily (QD) on Days 1 to Day 14 and a single oral dose of TAK-788 20 mg capsule was coadministered on Day 5 in Period 2.TAK-788 20 mg, capsule, at Hour 0 on Day 1 followed by an overnight fast in Period 1.
Overall Number of Participants Analyzed 12121212
Measure Type: Median (Full Range)
Unit of Measure: hr
2.00
(1.03 to 6.0)
6.00
(2.01 to 6.0)
8.00
(6.0 to 12.0)
6.00
(2.0 to 6.01)
3. PrimaryOutcome
Title Tmax - Time to Reach the Maximum Plasma Concentration (Cmax) of TAK-788
Description
Time Frame Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose
Outcome Measure Data
Analysis Population Description
PK Set included participants who complied sufficiently with the protocol and display an evaluable PK profile.
 
Arm/Group title Part 2, Treatment DPart 2, Treatment CPart 1, Treatment BPart 1, Treatment A
Arm/Group Description Following Treatment C, participants received rifampin 600 mg as capsules, orally, once daily (QD) on Days 1 to 13 and TAK-788 160 mg as capsules, orally was coadministered on Day 7 in Period 2.TAK-788 160 mg, orally, at Hour 0 on Day 1 following an overnight fast in Period 1.Following Treatment A, participants received itraconazole 200 mg solution, orally, once daily (QD) on Days 1 to Day 14 and a single oral dose of TAK-788 20 mg capsule was coadministered on Day 5 in Period 2.TAK-788 20 mg, capsule, at Hour 0 on Day 1 followed by an overnight fast in Period 1.
Overall Number of Participants Analyzed 12121212
Measure Type: Median (Full Range)
Unit of Measure: hr
4.00
(1.03 to 6.0)
6.00
(4.0 to 8.0)
8.00
(5.99 to 12.0)
6.00
(2.0 to 8.0)
4. PrimaryOutcome
Title Treatment D Vs Treatment C (Part 2), Combined Molar Exposure for AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity, Calculated Using the Observed Value of the Last Quantifiable Concentration of TAK-788, AP32960, and AP32914
Description The combined molar exposure AUC∞ for TAK-788 and its metabolites AP32960 and AP3914 value was calculated as the sum of each molar AUC∞ which was multiplied by 1000 and divided by molecular weight of each analyte, TAK-788, AP32960, and AP32914 respectively. The combined molar exposure was presented in hour*nanomolar.
Time Frame Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Outcome Measure Data
Analysis Population Description
PK Set included participants who complied sufficiently with the protocol and display an evaluable PK profile. Overall number analyzed is the number of participants with data available for analyses. Overall number analyzed is the number of participants with data available for analyses.
 
Arm/Group title Part 2, Treatment DPart 2, Treatment C
Arm/Group Description Following Treatment C, participants received rifampin 600 mg as capsules, orally, once daily (QD) on Days 1 to 13 and TAK-788 160 mg as capsules, orally was coadministered on Day 7 in Period 2.TAK-788 160 mg, orally, at Hour 0 on Day 1 following an overnight fast in Period 1.
Overall Number of Participants Analyzed 1112
Measure Type: Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hr*nM
194
3610
Statistical Analysis Overview Comparison Group Selection Tmax - Time to Reach the Maximum Plasma Concentration (Cmax) of AP32914, Tmax - Time to Reach the Maximum Plasma Concentration (Cmax) of AP32960, Tmax - Time to Reach the Maximum Plasma Concentration (Cmax) of TAK-788, Treatment D Vs Treatment C (Part 2), Combined Molar Exposure for AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity, Calculated Using the Observed Value of the Last Quantifiable Concentration of TAK-788, AP32960, and AP32914
Comments
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric LS Mean Ratio
Estimated Value 0.05
Confidence Interval (2-Sided ) 90.0%
0.04 to 0.07
Estimation Comments Linear mixed-effects model was used for analysis, using fixed-effect (treatment) and random-effect (participants). GMR and 90% CI was calculated using exponentiation of treatment LSMs difference.
5. PrimaryOutcome
Title Treatment B Vs Treatment A (Part 1), Combined Molar Exposure for AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity, Calculated Using the Observed Value of the Last Quantifiable Concentration of TAK-788, AP32960, and AP32914
Description The combined molar exposure AUC∞ for TAK-788 and its metabolites AP32960 and AP3914 value was calculated as the sum of each molar AUC∞ which was multiplied by 1000 and divided by molecular weight of each analyte, TAK-788, AP32960, and AP32914 respectively. The combined molar exposure was presented in hour*nanomolar.
Time Frame Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose
Outcome Measure Data
Analysis Population Description
PK Set included participants who complied sufficiently with the protocol and display an evaluable PK profile. Overall number analyzed is the number of participants with data available for analyses.
 
Arm/Group title Part 1, Treatment BPart 1, Treatment A
Arm/Group Description Following Treatment A, participants received itraconazole 200 mg solution, orally, once daily (QD) on Days 1 to Day 14 and a single oral dose of TAK-788 20 mg capsule was coadministered on Day 5 in Period 2.TAK-788 20 mg, capsule, at Hour 0 on Day 1 followed by an overnight fast in Period 1.
Overall Number of Participants Analyzed 108
Measure Type: Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hr*nM
1820
298
Statistical Analysis Overview Comparison Group Selection Tmax - Time to Reach the Maximum Plasma Concentration (Cmax) of AP32914, Tmax - Time to Reach the Maximum Plasma Concentration (Cmax) of AP32960, Tmax - Time to Reach the Maximum Plasma Concentration (Cmax) of TAK-788, Treatment D Vs Treatment C (Part 2), Combined Molar Exposure for AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity, Calculated Using the Observed Value of the Last Quantifiable Concentration of TAK-788, AP32960, and AP32914, Treatment B Vs Treatment A (Part 1), Combined Molar Exposure for AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity, Calculated Using the Observed Value of the Last Quantifiable Concentration of TAK-788, AP32960, and AP32914
Comments
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric LS Mean Ratio
Estimated Value 6.27
Confidence Interval (2-Sided ) 90.0%
5.2 to 7.56
Estimation Comments Linear mixed-effects model was used for analysis, using fixed-effect (treatment) and random-effect (participants). GMR and 90% CI was calculated using exponentiation of treatment LSMs difference.
6. PrimaryOutcome
Title Treatment D Vs Treatment C (Part 2), Combined Molar Exposure for Cmax: Maximum Observed Plasma Concentration of TAK-788, AP32960, and AP32914
Description The combined molar exposure Cmax for TAK-788 and its metabolites AP32960 and AP3914 value was calculated as the sum of each molar Cmax which was multiplied by 1000 and divided by molecular weight of each analyte, TAK-788, AP32960, and AP32914 respectively. The combined molar exposure was presented in nanomolar.
Time Frame Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Outcome Measure Data
Analysis Population Description
PK Set included participants who complied sufficiently with the protocol and display an evaluable PK profile.
 
Arm/Group title Part 2, Treatment DPart 2, Treatment C
Arm/Group Description Following Treatment C, participants received rifampin 600 mg as capsules, orally, once daily (QD) on Days 1 to 13 and TAK-788 160 mg as capsules, orally was coadministered on Day 7 in Period 2.TAK-788 160 mg, orally, at Hour 0 on Day 1 following an overnight fast in Period 1.
Overall Number of Participants Analyzed 1212
Measure Type: Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nM
14.9
177
Statistical Analysis Overview Comparison Group Selection Tmax - Time to Reach the Maximum Plasma Concentration (Cmax) of AP32914, Tmax - Time to Reach the Maximum Plasma Concentration (Cmax) of AP32960, Tmax - Time to Reach the Maximum Plasma Concentration (Cmax) of TAK-788, Treatment D Vs Treatment C (Part 2), Combined Molar Exposure for AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity, Calculated Using the Observed Value of the Last Quantifiable Concentration of TAK-788, AP32960, and AP32914, Treatment B Vs Treatment A (Part 1), Combined Molar Exposure for AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity, Calculated Using the Observed Value of the Last Quantifiable Concentration of TAK-788, AP32960, and AP32914, Treatment D Vs Treatment C (Part 2), Combined Molar Exposure for Cmax: Maximum Observed Plasma Concentration of TAK-788, AP32960, and AP32914
Comments
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric LS Mean Ratio
Estimated Value 0.08
Confidence Interval (2-Sided ) 90.0%
0.07 to 0.11
Estimation Comments Linear mixed-effects model was used for analysis, using fixed-effect (treatment) and random-effect (participants). GMR and 90% CI was calculated using exponentiation of treatment LSMs difference.
7. PrimaryOutcome
Title Treatment B vs Treatment A (Part 1), Combined Molar Exposure for Cmax: Maximum Observed Plasma Concentration of TAK-788, AP32960, and AP32914
Description The combined molar exposure Cmax for TAK-788 and its metabolites AP32960 and AP3914 value was calculated as the sum of each molar Cmax which was multiplied by 1000 and divided by molecular weight of each analyte, TAK-788, AP32960, and AP32914 respectively. The combined molar exposure was presented in nanomolar.
Time Frame Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose
Outcome Measure Data
Analysis Population Description
Pharmacokinetic (PK) Set included participants who complied sufficiently with the protocol and display an evaluable PK profile.
 
Arm/Group title Part 1, Treatment BPart 1, Treatment A
Arm/Group Description Following Treatment A, participants received itraconazole 200 mg solution, orally, once daily (QD) on Days 1 to Day 14 and a single oral dose of TAK-788 20 mg capsule was coadministered on Day 5 in Period 2.TAK-788 20 mg, capsule, at Hour 0 on Day 1 followed by an overnight fast in Period 1.
Overall Number of Participants Analyzed 1212
Measure Type: Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nM
39.2
13.7
Statistical Analysis Overview Comparison Group Selection Tmax - Time to Reach the Maximum Plasma Concentration (Cmax) of AP32914, Tmax - Time to Reach the Maximum Plasma Concentration (Cmax) of AP32960, Tmax - Time to Reach the Maximum Plasma Concentration (Cmax) of TAK-788, Treatment D Vs Treatment C (Part 2), Combined Molar Exposure for AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity, Calculated Using the Observed Value of the Last Quantifiable Concentration of TAK-788, AP32960, and AP32914, Treatment B Vs Treatment A (Part 1), Combined Molar Exposure for AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity, Calculated Using the Observed Value of the Last Quantifiable Concentration of TAK-788, AP32960, and AP32914, Treatment D Vs Treatment C (Part 2), Combined Molar Exposure for Cmax: Maximum Observed Plasma Concentration of TAK-788, AP32960, and AP32914, Treatment B vs Treatment A (Part 1), Combined Molar Exposure for Cmax: Maximum Observed Plasma Concentration of TAK-788, AP32960, and AP32914
Comments
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Least Squares (LS) Mean Ratio
Estimated Value 2.86
Confidence Interval (2-Sided ) 90.0%
2.48 to 3.3
Estimation Comments Linear mixed-effects model was used for analysis, using fixed-effect(treatment), random-effect(participants). Geometric mean ratios(GMR), 90% confidence interval(CI) calculated using exponentiation of treatment least squares means(LSMs) difference.
Adverse Events
Time Frame From first dose up to 30 days post last dose of study drug (Up to 45 days)
Adverse Event Reporting Description At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
 
Arm/Group Title Part 2, Treatment CPart 1, Treatment BPart 1, Treatment APart 2, Treatment D
Arm/Group Description TAK-788 160 mg, orally, at Hour 0 on Day 1 following an overnight fast in Period 1.Following Treatment A, participants received itraconazole 200 mg solution, orally, once daily (QD) on Days 1 to Day 14 and a single oral dose of TAK-788 20 mg capsule was coadministered on Day 5 in Period 2.TAK-788 20 mg, capsule, at Hour 0 on Day 1 followed by an overnight fast in Period 1.Following Treatment C, participants received rifampin 600 mg as capsules, orally, once daily (QD) on Days 1 to 13 and TAK-788 160 mg as capsules, orally was coadministered on Day 7 in Period 2.
All-Cause Mortality
  Part 1, Treatment A Part 1, Treatment B Part 2, Treatment C Part 2, Treatment D
Affected at Risk (%) Affected at Risk (%) Affected at Risk (%) Affected at Risk (%)
Total 0/12 (0.00%) 0/12 (0.00%) 0/12 (0.00%) 0/12 (0.00%)
Total
Total, all-cause mortality 0 /12 (0.00%) 0 /12 (0.00%) 0 /12 (0.00%) 0 /12 (0.00%)
Serious Adverse Events
  Part 1, Treatment A Part 1, Treatment B Part 2, Treatment C Part 2, Treatment D
Affected at Risk (%) Affected at Risk (%) Affected at Risk (%) Affected at Risk (%)
Total 0/12 (0.00%) 0/12 (0.00%) 0/12 (0.00%) 0/12 (0.00%)
Total
Total, serious adverse events 0 /12 (0.00%) 0 /12 (0.00%) 0 /12 (0.00%) 0 /12 (0.00%)
Show Other (Not Including Serious) Adverse Events
  Part 1, Treatment A Part 1, Treatment B Part 2, Treatment C Part 2, Treatment D
Affected at Risk (%) Affected at Risk (%) Affected at Risk (%) Affected at Risk (%)
Total 1/12 (8.33%) 4/12 (33.33%) 9/12 (75.00%) 10/12 (83.33%)
Ear and labyrinth disorders
Ear pain 0 /12 (0.00%) 0 /12 (0.00%) 0 /12 (0.00%) 1 /12 (8.33%)
Gastrointestinal disorders
Vomiting 0 /12 (0.00%) 1 /12 (8.33%) 0 /12 (0.00%) 0 /12 (0.00%)
Oral discomfort 0 /12 (0.00%) 0 /12 (0.00%) 0 /12 (0.00%) 1 /12 (8.33%)
Nausea 0 /12 (0.00%) 0 /12 (0.00%) 1 /12 (8.33%) 2 /12 (16.67%)
Lip dry 0 /12 (0.00%) 0 /12 (0.00%) 0 /12 (0.00%) 1 /12 (8.33%)
Flatulence 0 /12 (0.00%) 1 /12 (8.33%) 0 /12 (0.00%) 0 /12 (0.00%)
Diarrhoea 0 /12 (0.00%) 2 /12 (16.67%) 2 /12 (16.67%) 3 /12 (25.00%)
Abdominal pain lower 0 /12 (0.00%) 0 /12 (0.00%) 0 /12 (0.00%) 1 /12 (8.33%)
Abdominal pain 0 /12 (0.00%) 0 /12 (0.00%) 0 /12 (0.00%) 1 /12 (8.33%)
Abdominal distension 0 /12 (0.00%) 1 /12 (8.33%) 0 /12 (0.00%) 0 /12 (0.00%)
General disorders
Feeling hot 0 /12 (0.00%) 0 /12 (0.00%) 1 /12 (8.33%) 1 /12 (8.33%)
Chills 0 /12 (0.00%) 1 /12 (8.33%) 0 /12 (0.00%) 1 /12 (8.33%)
Chest discomfort 0 /12 (0.00%) 0 /12 (0.00%) 0 /12 (0.00%) 2 /12 (16.67%)
Infections and infestations
Urinary tract infection 0 /12 (0.00%) 0 /12 (0.00%) 0 /12 (0.00%) 1 /12 (8.33%)
Injury, poisoning and procedural complications
Limb injury 0 /12 (0.00%) 0 /12 (0.00%) 0 /12 (0.00%) 1 /12 (8.33%)
Musculoskeletal and connective tissue disorders
Back pain 0 /12 (0.00%) 1 /12 (8.33%) 1 /12 (8.33%) 1 /12 (8.33%)
Nervous system disorders
Sensory disturbance 0 /12 (0.00%) 1 /12 (8.33%) 0 /12 (0.00%) 0 /12 (0.00%)
Paraesthesia 0 /12 (0.00%) 0 /12 (0.00%) 1 /12 (8.33%) 0 /12 (0.00%)
Headache 0 /12 (0.00%) 1 /12 (8.33%) 1 /12 (8.33%) 2 /12 (16.67%)
Dysgeusia 0 /12 (0.00%) 0 /12 (0.00%) 0 /12 (0.00%) 1 /12 (8.33%)
Dizziness 0 /12 (0.00%) 0 /12 (0.00%) 1 /12 (8.33%) 0 /12 (0.00%)
Burning sensation 0 /12 (0.00%) 0 /12 (0.00%) 0 /12 (0.00%) 1 /12 (8.33%)
Renal and urinary disorders
Micturition urgency 0 /12 (0.00%) 0 /12 (0.00%) 0 /12 (0.00%) 1 /12 (8.33%)
Reproductive system and breast disorders
Menstruation delayed 0 /12 (0.00%) 0 /12 (0.00%) 1 /12 (8.33%) 0 /12 (0.00%)
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain 0 /12 (0.00%) 0 /12 (0.00%) 0 /12 (0.00%) 2 /12 (16.67%)
Dyspnoea 0 /12 (0.00%) 0 /12 (0.00%) 0 /12 (0.00%) 1 /12 (8.33%)
Dry throat 0 /12 (0.00%) 0 /12 (0.00%) 2 /12 (16.67%) 0 /12 (0.00%)
Skin and subcutaneous tissue disorders
Rash papular 0 /12 (0.00%) 0 /12 (0.00%) 0 /12 (0.00%) 1 /12 (8.33%)
Rash 0 /12 (0.00%) 0 /12 (0.00%) 0 /12 (0.00%) 2 /12 (16.67%)
Pruritus generalised 0 /12 (0.00%) 0 /12 (0.00%) 2 /12 (16.67%) 0 /12 (0.00%)
Pruritus 0 /12 (0.00%) 0 /12 (0.00%) 0 /12 (0.00%) 2 /12 (16.67%)
Generalised erythema 0 /12 (0.00%) 0 /12 (0.00%) 1 /12 (8.33%) 0 /12 (0.00%)
Dry skin 1 /12 (8.33%) 0 /12 (0.00%) 3 /12 (25.00%) 0 /12 (0.00%)
Total
Total, other adverse events 1 /12 (8.33%) 4 /12 (33.33%) 9 /12 (75.00%) 10 /12 (83.33%)
Vascular disorders
Flushing 0 /12 (0.00%) 0 /12 (0.00%) 1 /12 (8.33%) 0 /12 (0.00%)
Limitations and Caveats

[Not Specified]

More Information
Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

In general, Investigators may publish clinical data after the earlier of (i) publication by the Sponsor or (ii) 12 months following the abandonment, early termination or database lock; provided a copy of the publication provided to Sponsor at least 30 days ahead of publication, the Sponsor's confidential information is removed as may be requested by Sponsor and Investigator defers publication for up to 60 days in the event Sponsor provides notice that it intends to file a patent application.

Results Point of Contact
  • ClinicalTrials.gov Identifier: NCT03928327 History of Changes
  • Other Study ID Numbers: TAK-788-1006
  • First Submitted: April 24, 2019
  • First Posted: April 26, 2019
  • Results First Submitted: August 11, 2020
  • Results First Posted: August 21, 2020
  • Last Update Posted: August 21, 2020