Clinical trial NCT03919890: A Two-Part Study to Assess the Safety, Tolerability, PK and PD of ONO-7684 in Healthy Adult Volunteers
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Venous Thromboembolism
Lead sponsor: Ono Pharmaceutical Co. Ltd
Sponsor class: INDUSTRY
First posted: 2019-04-18
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Number of participants with clinically significant changes in vital signs (Part A & B)
timeFrame: Part A: Day 1-4 & Follow-up and Part B: Day 1-15, 17 & Follow up
measure: Number of participants with clinically significant changes observed on 12-lead electrocardiogram (ECG) (Part A & B)
timeFrame: Part A: Day 1-4 & Follow up & Part B: Day 1,3,5,7,9,11,14,17 & Follow up
measure: Number of participants with clinically significant changes in cardiac telemetry (Part A only)
timeFrame: Part A: From 0.5-1 hours pre-dose until 12 hours after dosing at Day 1
measure: Number of participants with clinically significant changes in physical examination (Part A & B)
timeFrame: Part A: Day -1, 1-4 & Follow-up and Part B: Day-1, 1-17 & Follow up
measure: Number of participants with clinically significant changes in laboratory safety tests (haematology, biochemistry and urinalysis) (Part A & B)
timeFrame: Part A: Day-1, 1-4 & Follow up and Part B: Day-1, 1-17 & Follow up
measure: Number of participants with adverse events (AE) (Part A & B)
timeFrame: Part A: Day-1, 1-4 & Follow up and Part B: Day-1, 1-17 & Follow up
Secondary outcomes:
measure: Pharmacokinetics (Cmax)
timeFrame: Part A: Day 1 through Day 4. Part B: Day 1 and Day 14
measure: Pharmacokinetics (tmax)
timeFrame: Part A: Day 1 through Day 4. Part B: Day 1 and Day 14
measure: Pharmacokinetics (AUClast)
timeFrame: Part A: Day 1 through Day 4. Part B: Day 14
measure: Pharmacokinetics (AUCinf)
timeFrame: Part A: Day 1 through Day 4. Part B: Day 14
measure: Pharmacokinetics (AUCt)
timeFrame: Part A: Day 1 through Day 4. Part B: Day 1
measure: Pharmacokinetics (%AUCextrap)
timeFrame: Part A: Day 1 through Day 4. Part B: Day 14
measure: Pharmacokinetics (t1/2)
timeFrame: Part A: Day 1 through Day 4. Part B: Day 14
measure: Pharmacokinetics (CL/F)
timeFrame: Day 1 through Day 4
measure: Pharmacokinetics (Terminal Rate Constant)
timeFrame: Day 1 through Day 4
measure: Pharmacokinetics (Aet)
timeFrame: Day 1 through Day 4
measure: Pharmacokinetic (fe/F)
timeFrame: Day 1 through Day 4
measure: Pharmacokinetic (CLr)
timeFrame: Day 1 through Day 4
measure: Pharmacokinetic (Ctrough)
timeFrame: Day 1 through Day 14
measure: Pharmacokinetic (AUCtau)
timeFrame: Day 14
measure: Pharmacokinetic (CLSS/F)
timeFrame: Day 14
measure: Pharmacokinetic (VZ/F)
timeFrame: Day 14
measure: Pharmacodynamic (change from baseline in aPTT activity) in serum
timeFrame: Part A: Day 1 through Day 4. Part B: Day 1 through Day 17
measure: Pharmacodynamic (change from baseline in PT activity) in serum
timeFrame: Part A: Day 1 through Day 4. Part B: Day 1 through Day 17
measure: Pharmacodynamic (change from baseline in PT-INR activity) in serum
timeFrame: Part A: Day 1 through Day 4. Part B: Day 1 through Day 17
measure: Pharmacodynamic (change from baseline in FXIa activity) in serum
timeFrame: Part A: Day 1 through Day 4. Part B: Day 1 through Day 17
measure: Pharmacodynamic (correlation of aPTT and FXIa activity) in serum
timeFrame: Part A: Day 1 through Day 4. Part B: Day 1 through Day 17
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Hammersmith Medicines Research (HMR)
Study officials:
References: