Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03919890
Recruitment Status : Recruiting
First Posted : April 18, 2019
Last Update Posted : April 18, 2019
Sponsor:
Information provided by (Responsible Party):
Ono Pharmaceutical Co. Ltd

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 Intervention/treatment Phase
Venous Thromboembolism Drug: ONO-7684 Drug: ONO-7684 Placebo 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double (Participant, Investigator)
Masking Description: Double-blinded
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 17, 2019
Estimated Primary Completion Date : July 26, 2019
Estimated Study Completion Date : July 26, 2019

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

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

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

Placebo Comparator: ONO-7684 Placebo Part A2
Single doses of ONO-7684 or placebo orally under fed conditions
Drug: ONO-7684 Placebo
Placebo comparator

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 B1
Eligible subjects will receive multiple doses of ONO-7684 or placebo orally
Drug: ONO-7684 Placebo
Placebo comparator




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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03919890


Contacts
Layout table for location contacts
Contact: ONO Pharma UK, Ltd +44 2074214920 ctinfo@ono-uk.co.uk

Locations
Layout table for location information
United Kingdom
Hammersmith Medicines Research (HMR) Recruiting
London, United Kingdom, NW10 7EW
Contact: Malcolm Boyce, MD    +44 20 8961 4130    hmr@hmrlondon.com   
Principal Investigator: Malcolm Boyce, MD         
Sponsors and Collaborators
Ono Pharmaceutical Co. Ltd

Layout table for additonal 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: April 18, 2019
Last Verified: April 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Thromboembolism
Venous Thromboembolism
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases