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Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 01/16/2021.

A Two-Part Study to Assess the Safety, Tolerability, PK and PD of ONO-7684 in Healthy Adult Volunteers

Clinicaltrials.gov identifier NCT03919890

Recruitment Status Completed

First Posted April 18, 2019

Last update posted December 9, 2019

Study Description

Brief summary:

This is a first in human study to determine the safety, tolerability, pharmacokinetics and pharmacodynamics of ONO-7684 in healthy adult volunteers. This study will be conducted in 2 parts: Part A is a single-ascending dose and Part B is a multiple-ascending dose.

  • Condition or Disease:Venous Thromboembolism
  • Intervention/Treatment: Drug: ONO-7684 Placebo
    Drug: ONO-7684
  • Phase: Phase 1
Detailed Description

This study aims to obtain safety, tolerability, pharmacokinetic and pharmacodynamic data when ONO-7684 is administered orally as single doses and as multiple doses to healthy subjects. The study will consist of 2 parts: A single ascending dose (SAD) phase (Part A); a multiple ascending dose (MAD) phase (Part B). One cohort of Part A will receive ONO-7684 under both fasted and fed conditions to investigate the effect of food.

Study Design
  • Study Type: Interventional
  • Actual Enrollment: 72 participants
  • Allocation: Randomized
  • Intervention Model: Sequential Assignment
  • Masking: Double (Participant, Investigator)
  • Primary Purpose: Treatment
  • Official Title: A First-in-human, Randomised, Placebo-controlled, Double-blind, Single and Multiple Dose Study to Explore the Safety, Tolerability, PK and PD of Oral Doses of ONO-7684 in Healthy Subjects Under Fed and Fasted Conditions
  • Actual Study Start Date: January 2019
  • Actual Primary Completion Date: August 2019
  • Actual Study Completion Date: August 2019
Arms and interventions
Arm Intervention/treatment
Experimental: ONO-7684 Part A1
Single ascending doses of ONO-7684 or placebo orally under fasted conditions
Drug: ONO-7684
Single ascending doses for cohorts A1-A8 and multiple ascending doses cohorts B1-3
Experimental: ONO-7684 Part A2
Single doses of ONO-7684 or placebo orally under fed conditions
Drug: ONO-7684
Single ascending doses for cohorts A1-A8 and multiple ascending doses cohorts B1-3
Experimental: ONO-7684 Part B1
Eligible subjects will receive multiple doses of ONO-7684 or placebo orally
Drug: ONO-7684
Single ascending doses for cohorts A1-A8 and multiple ascending doses cohorts B1-3
Placebo Comparator: ONO-7684 Placebo Part A1
Single ascending doses of ONO-7684 or placebo orally under fasted conditions
Drug: ONO-7684 Placebo
Placebo comparator
Placebo Comparator: ONO-7684 Placebo Part A2
Single doses of ONO-7684 or placebo orally under fed conditions
Drug: ONO-7684 Placebo
Placebo comparator
Placebo Comparator: ONO-7684 Placebo Part B1
Eligible subjects will receive multiple doses of ONO-7684 or placebo orally
Drug: ONO-7684 Placebo
Placebo comparator
Outcome Measures
  • Primary Outcome Measures: 1. Number of participants with clinically significant changes in vital signs (Part A & B) [ Time Frame: Part A: Day 1-4 & Follow-up and Part B: Day 1-15, 17 & Follow up ]
    Pulse rate (bpm), systolic and diastolic blood pressure (mmHg), Respiratory rate (bpm)
  • 2. Number of participants with clinically significant changes observed on 12-lead electrocardiogram (ECG) (Part A & B) [ Time Frame: Part A: Day 1-4 & Follow up & Part B: Day 1,3,5,7,9,11,14,17 & Follow up ]
    Ventricular rate (beats/min), PR interval (msec), QRS interval (msec), QT (msec), QTcF interval (msec)
  • 3. Number of participants with clinically significant changes in cardiac telemetry (Part A only) [ Time Frame: Part A: From 0.5-1 hours pre-dose until 12 hours after dosing at Day 1 ]
    Number of participants with cardiac telemetry abnormalities will be reported.
  • 4. Number of participants with clinically significant changes in physical examination (Part A & B) [ Time Frame: Part A: Day -1, 1-4 & Follow-up and Part B: Day-1, 1-17 & Follow up ]
    Number of participants with physical examination abnormalities will be reported.
  • 5. Number of participants with clinically significant changes in laboratory safety tests (haematology, biochemistry and urinalysis) (Part A & B) [ Time Frame: Part A: Day-1, 1-4 & Follow up and Part B: Day-1, 1-17 & Follow up ]
    Number of participants with abnormalities in laboratory safety tests will be reported.
  • 6. Number of participants with adverse events (AE) (Part A & B) [ Time Frame: Part A: Day-1, 1-4 & Follow up and Part B: Day-1, 1-17 & Follow up ]
    AE is any untoward medical occurrence in a subject or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
  • Secondary Outcome Measures: 1. Pharmacokinetics (Cmax) [ Time Frame: Part A: Day 1 through Day 4. Part B: Day 1 and Day 14 ]
    Assessment of the maximum observed plasma concentration of ONO-7684 and 3-hydroxybenzoic acid in Parts A and B
  • 2. Pharmacokinetics (tmax) [ Time Frame: Part A: Day 1 through Day 4. Part B: Day 1 and Day 14 ]
    Assessment of the maximum observed plasma concentration of ONO-7684 and 3-hydroxybenzoic acid in Parts A and B
  • 3. Pharmacokinetics (AUClast) [ Time Frame: Part A: Day 1 through Day 4. Part B: Day 14 ]
    Assessment of the area under the curve of ONO-7684 and 3-hydroxybenzoic acid in Parts A and B
  • 4. Pharmacokinetics (AUCinf) [ Time Frame: Part A: Day 1 through Day 4. Part B: Day 14 ]
    Assessment of the area under the curve of ONO-7684 and 3-hydroxybenzoic acid in Parts A and B
  • 5. Pharmacokinetics (AUCt) [ Time Frame: Part A: Day 1 through Day 4. Part B: Day 1 ]
    Assessment of the area under the curve of concentration of ONO-7684 and 3-hydroxybenzoic acid - time from zero up to a definitive time, t in Parts A and B
  • 6. Pharmacokinetics (%AUCextrap) [ Time Frame: Part A: Day 1 through Day 4. Part B: Day 14 ]
    Assessment of the percentage of AUC∞ extrapolated from tlast to infinity of ONO-7684 and 3-hydroxybenzoic acid in Parts A and B
  • 7. Pharmacokinetics (t1/2) [ Time Frame: Part A: Day 1 through Day 4. Part B: Day 14 ]
    Assessment of the elimination half-time of ONO-7684 and 3-hydroxybenzoic acid in Parts A and B
  • 8. Pharmacokinetics (CL/F) [ Time Frame: Day 1 through Day 4 ]
    Assessment of the apparent clearance rate of ONO-7684 and 3-hydroxybenzoic acid in Part A only
  • 9. Pharmacokinetics (Terminal Rate Constant) [ Time Frame: Day 1 through Day 4 ]
    Assessment of the terminal rate constant (slowest rate constant of the disposition) of ONO-7684 and 3-hydroxybenzoic acid in plasma in Part A only
  • 10. Pharmacokinetics (Aet) [ Time Frame: Day 1 through Day 4 ]
    Assessment of the amount of ONO-7684 excreted in urine over the period of sample collection in Part A only
  • 11. Pharmacokinetic (fe/F) [ Time Frame: Day 1 through Day 4 ]
    Assessment of the fraction of orally administered ONO-7684 excreted into urine in Part A only
  • 12. Pharmacokinetic (CLr) [ Time Frame: Day 1 through Day 4 ]
    Assessment of the renal clearance of ONO-7684 from plasma in Part A only
  • 13. Pharmacokinetic (Ctrough) [ Time Frame: Day 1 through Day 14 ]
    Assessment of the trough plasma concentration of ONO-7684 and 3-hydroxybenzoic acid in Part B only
  • 14. Pharmacokinetic (AUCtau) [ Time Frame: Day 14 ]
    Assessment of the area under the plasma concentration of ONO-7684 and 3-hydroxybenzoic acid -time during a dosing interval in Part B only
  • 15. Pharmacokinetic (CLSS/F) [ Time Frame: Day 14 ]
    Assessment of total clearance of ONO-7684 from plasma after oral administration in Part B only
  • 16. Pharmacokinetic (VZ/F) [ Time Frame: Day 14 ]
    Assessment of apparent volume of distribution of ONO-7684 after non-intravenous administration calculated at steady state in Part B only
  • 17. Pharmacodynamic (change from baseline in aPTT activity) in serum [ Time Frame: Part A: Day 1 through Day 4. Part B: Day 1 through Day 17 ]
    Assessment of the effect of ONO-7684 in activated partial thromboplastin time in Parts A and B
  • 18. Pharmacodynamic (change from baseline in PT activity) in serum [ Time Frame: Part A: Day 1 through Day 4. Part B: Day 1 through Day 17 ]
    Assessment of the effect of ONO-7684 in prothrombin time in Parts A and B
  • 19. Pharmacodynamic (change from baseline in PT-INR activity) in serum [ Time Frame: Part A: Day 1 through Day 4. Part B: Day 1 through Day 17 ]
    Assessment of the effect of ONO-7684 in prothrombin time-international normalised ratio in Parts A and B
  • 20. Pharmacodynamic (change from baseline in FXIa activity) in serum [ Time Frame: Part A: Day 1 through Day 4. Part B: Day 1 through Day 17 ]
    Assessment of the effect of ONO-7684 in blood coagulation activated factor XI in Parts A and B
  • 21. Pharmacodynamic (correlation of aPTT and FXIa activity) in serum [ Time Frame: Part A: Day 1 through Day 4. Part B: Day 1 through Day 17 ]
    Assessment of the effect of ONO-7684 in the correlation of activated partial thromboplastin time to blood coagulation activated factor XI in Parts A and B
Eligibility Criteria
  • Ages Eligible for Study: 18 to 55 Years (Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers: Yes
Criteria

Inclusion Criteria:

1. 18-55 years

2. normotensive male volunteers, or female volunteers of non-childbearing potential (Part
B only)

3. body mass index 18.0-30.0 kg/m2

4. deemed healthy on the basis of a clinical history, physical examination, ECG, vital
signs, and laboratory tests of blood and urine

5. registered with a General Practitioner (GP) in the UK

6. agree to use an effective method of contraception

7. able to give fully informed written consent

Exclusion Criteria:

1. Positive tests for hepatitis B & C, HIV

2. severe adverse reaction to any drug

3. sensitivity to trial medication

4. drug or alcohol abuse

5. current smoker or use of nicotine containing products in the previous 6 months

6. vegetarians or vegans, or unwilling to eat a high-fat breakfast (Part A food effect
cohorts only)

7. use of strong CYP3A4/5 or P-glycoprotein inhibitors or inducers, anticoagulants,
antiplatelet agents, non-steroidal anti-inflammatory drugs and/or acetylsalicylic acid
within the previous 30 days

8. prescription or over-the-counter medication, vitamins, herbal treatments or dietary
supplements within the previous 7 days (with the exception of paracetamol
[acetaminophen])

9. participation in other clinical trials of unlicensed medicines, or loss of more than
400 mL blood, within the previous 3 months or plan to donate blood or blood products
in the 3 months after the trial

10. vital signs outside the acceptable range

11. clinically relevant abnormal findings at the screening assessment (including
creatinine clearance, haemoglobin levels and QTcF)

12. acute or chronic illness

13. clinically relevant abnormal medical history or concurrent medical condition

14. objection by GP

15. possibility that volunteer will not cooperate

16. pre-menopausal females who are pregnant or lactating, or who are of childbearing
potential

Contacts and Locations
Contacts
Locations

United Kingdom
Hammersmith Medicines Research (HMR)
London

Sponsors and Collaborators

Ono Pharmaceutical Co. Ltd

More Information
  • Responsible Party: Ono Pharmaceutical Co. Ltd
  • ClinicalTrials.gov Identifier: NCT03919890 History of Changes
  • Other Study ID Numbers: ONO-7684-01
  • First Posted: April 18, 2019 Key Record Dates
  • Last Update Posted: December 9, 2019
  • Last Verified: December 2019
  • Studies a U.S. FDA-regulated Drug Product: No
  • Studies a U.S. FDA-regulated Device Product: No
  • Additional relevant MeSH terms: Thromboembolism Venous Thromboembolism