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

December 6, 2019 updated by: Ono Pharmaceutical Co. Ltd

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
72

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • London, United Kingdom, NW10 7EW
        • Hammersmith Medicines Research (HMR)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 51 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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)
Part A: Day 1-4 & Follow-up and Part B: Day 1-15, 17 & Follow up
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)
Part A: Day 1-4 & Follow up & Part B: Day 1,3,5,7,9,11,14,17 & Follow up
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.
Part A: From 0.5-1 hours pre-dose until 12 hours after dosing at Day 1
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.
Part A: Day -1, 1-4 & Follow-up and Part B: Day-1, 1-17 & Follow up
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.
Part A: Day-1, 1-4 & Follow up and Part B: Day-1, 1-17 & Follow up
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.
Part A: Day-1, 1-4 & Follow up and Part B: Day-1, 1-17 & Follow up

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
Part A: Day 1 through Day 4. Part B: Day 1 and Day 14
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
Part A: Day 1 through Day 4. Part B: Day 1 and Day 14
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
Part A: Day 1 through Day 4. Part B: Day 14
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
Part A: Day 1 through Day 4. Part B: Day 14
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
Part A: Day 1 through Day 4. Part B: Day 1
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
Part A: Day 1 through Day 4. Part B: Day 14
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
Part A: Day 1 through Day 4. Part B: Day 14
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
Day 1 through Day 4
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
Day 1 through Day 4
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
Day 1 through Day 4
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
Day 1 through Day 4
Pharmacokinetic (CLr)
Time Frame: Day 1 through Day 4
Assessment of the renal clearance of ONO-7684 from plasma in Part A only
Day 1 through Day 4
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
Day 1 through Day 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
Day 14
Pharmacokinetic (CLSS/F)
Time Frame: Day 14
Assessment of total clearance of ONO-7684 from plasma after oral administration in Part B only
Day 14
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
Day 14
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
Part A: Day 1 through Day 4. Part B: Day 1 through Day 17
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
Part A: Day 1 through Day 4. Part B: Day 1 through Day 17
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
Part A: Day 1 through Day 4. Part B: Day 1 through Day 17
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
Part A: Day 1 through Day 4. Part B: Day 1 through Day 17
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
Part A: Day 1 through Day 4. Part B: Day 1 through Day 17

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Ono Pharmaceutical Co. Ltd

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 17, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 23, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 23, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 14, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 15, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 18, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 9, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 6, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ONO-7684-01

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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