Venous ThromboembolismPhase 1NCT03919890
A Two-Part Study to Assess the Safety, Tolerability, PK and PD of ONO-7684 in Healthy Adult Volunteers
A Phase 1 study testing ONO-7684 in people with Venous Thromboembolism, run by Ono Pharmaceutical Co., Ltd. at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Venous Thromboembolism
- What is being tested?
- ONO-7684
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 72 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 17 Jan 2019to 23 Aug 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 18-55 years
- normotensive male volunteers, or female volunteers of non-childbearing potential (Part B only)
- body mass index 18.0-30.0 kg/m2
- deemed healthy on the basis of a clinical history, physical examination, ECG, vital signs, and laboratory tests of blood and urine
- registered with a General Practitioner (GP) in the UK
- agree to use an effective method of contraception
- able to give fully informed written consent
Who cannot join
- Positive tests for hepatitis B \& C, HIV
- severe adverse reaction to any drug
- sensitivity to trial medication
- drug or alcohol abuse
- current smoker or use of nicotine containing products in the previous 6 months
- vegetarians or vegans, or unwilling to eat a high-fat breakfast (Part A food effect cohorts only)
Show all 16Show fewer
- 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
- prescription or over-the-counter medication, vitamins, herbal treatments or dietary supplements within the previous 7 days (with the exception of paracetamol [acetaminophen])
- 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
- vital signs outside the acceptable range
- clinically relevant abnormal findings at the screening assessment (including creatinine clearance, haemoglobin levels and QTcF)
- acute or chronic illness
- clinically relevant abnormal medical history or concurrent medical condition
- objection by GP
- possibility that volunteer will not cooperate
- pre-menopausal females who are pregnant or lactating, or who are of childbearing potential
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Hammersmith Medicines Research (HMR)
London, NW10 7EW
About this study
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
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.
Read the 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.
- Conditions
- Venous Thromboembolism
- Being tested
- ONO-7684, ONO-7684 Placebo
- Medical subject headings
- Venous Thromboembolism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ONO-7684Drug
Single ascending doses for cohorts A1-A8 and multiple ascending doses cohorts B1-3
ONO-7684 PlaceboDrug
Placebo comparator
| Study group | Role | What they receive |
|---|---|---|
| ONO-7684 Part A1 | Experimental | Single ascending doses of ONO-7684 or placebo orally under fasted conditions Receives: Drug: ONO-7684 |
| ONO-7684 Placebo Part A1 | Placebo comparator | Single ascending doses of ONO-7684 or placebo orally under fasted conditions Receives: Drug: ONO-7684 Placebo |
| ONO-7684 Part A2 | Experimental | Single doses of ONO-7684 or placebo orally under fed conditions Receives: Drug: ONO-7684 |
| ONO-7684 Placebo Part A2 | Placebo comparator | Single doses of ONO-7684 or placebo orally under fed conditions Receives: Drug: ONO-7684 Placebo |
| ONO-7684 Part B1 | Experimental | Eligible subjects will receive multiple doses of ONO-7684 or placebo orally Receives: Drug: ONO-7684 |
| ONO-7684 Placebo Part B1 | Placebo comparator | Eligible subjects will receive multiple doses of ONO-7684 or placebo orally Receives: Drug: ONO-7684 Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with clinically significant changes in vital signs (Part A & B)
Pulse rate (bpm), systolic and diastolic blood pressure (mmHg), Respiratory rate (bpm)
Measured: 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)
Ventricular rate (beats/min), PR interval (msec), QRS interval (msec), QT (msec), QTcF interval (msec)
Measured: 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)
Number of participants with cardiac telemetry abnormalities will be reported.
Measured: 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)
Number of participants with physical examination abnormalities will be reported.
Measured: 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)
Number of participants with abnormalities in laboratory safety tests will be reported.
Measured: 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)
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.
Measured: Part A: Day-1, 1-4 & Follow up and Part B: Day-1, 1-17 & Follow up
Secondary outcomes (21)
Pharmacokinetics (Cmax)
Assessment of the maximum observed plasma concentration of ONO-7684 and 3-hydroxybenzoic acid in Parts A and B
Measured: Part A: Day 1 through Day 4. Part B: Day 1 and Day 14
Pharmacokinetics (tmax)
Assessment of the maximum observed plasma concentration of ONO-7684 and 3-hydroxybenzoic acid in Parts A and B
Measured: Part A: Day 1 through Day 4. Part B: Day 1 and Day 14
Pharmacokinetics (AUClast)
Assessment of the area under the curve of ONO-7684 and 3-hydroxybenzoic acid in Parts A and B
Measured: Part A: Day 1 through Day 4. Part B: Day 14
Pharmacokinetics (AUCinf)
Assessment of the area under the curve of ONO-7684 and 3-hydroxybenzoic acid in Parts A and B
Measured: Part A: Day 1 through Day 4. Part B: Day 14
Pharmacokinetics (AUCt)
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
Measured: Part A: Day 1 through Day 4. Part B: Day 1
Pharmacokinetics (%AUCextrap)
Assessment of the percentage of AUC∞ extrapolated from tlast to infinity of ONO-7684 and 3-hydroxybenzoic acid in Parts A and B
Measured: Part A: Day 1 through Day 4. Part B: Day 14
Pharmacokinetics (t1/2)
Assessment of the elimination half-time of ONO-7684 and 3-hydroxybenzoic acid in Parts A and B
Measured: Part A: Day 1 through Day 4. Part B: Day 14
Pharmacokinetics (CL/F)
Assessment of the apparent clearance rate of ONO-7684 and 3-hydroxybenzoic acid in Part A only
Measured: Day 1 through Day 4
Pharmacokinetics (Terminal Rate Constant)
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
Measured: Day 1 through Day 4
Pharmacokinetics (Aet)
Assessment of the amount of ONO-7684 excreted in urine over the period of sample collection in Part A only
Measured: Day 1 through Day 4
Pharmacokinetic (fe/F)
Assessment of the fraction of orally administered ONO-7684 excreted into urine in Part A only
Measured: Day 1 through Day 4
Pharmacokinetic (CLr)
Assessment of the renal clearance of ONO-7684 from plasma in Part A only
Measured: Day 1 through Day 4
Pharmacokinetic (Ctrough)
Assessment of the trough plasma concentration of ONO-7684 and 3-hydroxybenzoic acid in Part B only
Measured: Day 1 through Day 14
Pharmacokinetic (AUCtau)
Assessment of the area under the plasma concentration of ONO-7684 and 3-hydroxybenzoic acid -time during a dosing interval in Part B only
Measured: Day 14
Pharmacokinetic (CLSS/F)
Assessment of total clearance of ONO-7684 from plasma after oral administration in Part B only
Measured: Day 14
Pharmacokinetic (VZ/F)
Assessment of apparent volume of distribution of ONO-7684 after non-intravenous administration calculated at steady state in Part B only
Measured: Day 14
Pharmacodynamic (change from baseline in aPTT activity) in serum
Assessment of the effect of ONO-7684 in activated partial thromboplastin time in Parts A and B
Measured: Part A: Day 1 through Day 4. Part B: Day 1 through Day 17
Pharmacodynamic (change from baseline in PT activity) in serum
Assessment of the effect of ONO-7684 in prothrombin time in Parts A and B
Measured: Part A: Day 1 through Day 4. Part B: Day 1 through Day 17
Pharmacodynamic (change from baseline in PT-INR activity) in serum
Assessment of the effect of ONO-7684 in prothrombin time-international normalised ratio in Parts A and B
Measured: Part A: Day 1 through Day 4. Part B: Day 1 through Day 17
Pharmacodynamic (change from baseline in FXIa activity) in serum
Assessment of the effect of ONO-7684 in blood coagulation activated factor XI in Parts A and B
Measured: Part A: Day 1 through Day 4. Part B: Day 1 through Day 17
Pharmacodynamic (correlation of aPTT and FXIa activity) in serum
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
Measured: Part A: Day 1 through Day 4. Part B: Day 1 through Day 17
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2019
- Study start17 Jan 2019
- Primary completion23 Aug 2019
- Study completion23 Aug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Venous ThromboembolismStudies of the same condition, open and under way.
- More trials run by Ono Pharmaceutical Co., Ltd.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ono Pharmaceutical Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03919890
- Sponsor's protocol ID
- ONO-7684-01
- Status last verified
- Dec 2019
- First submitted
- 14 Mar 2019
- Last updated
- 9 Dec 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03919890
- Acronym / sponsor ID
- ONO-7684-01
- Conditions
- Venous Thromboembolism
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- Ono Pharmaceutical Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- 17 Jan 2019 (actual)
- Primary completion
- 23 Aug 2019 (actual)
- Study completion
- 23 Aug 2019 (actual)
- First posted
- 18 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind (participant, investigator)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| ONO-7684 Part A1 | Experimental | Drug: ONO-7684Single ascending doses of ONO-7684 or placebo orally under fasted conditions |
| ONO-7684 Placebo Part A1 | Placebo comparator | Drug: ONO-7684 PlaceboSingle ascending doses of ONO-7684 or placebo orally under fasted conditions |
| ONO-7684 Part A2 | Experimental | Drug: ONO-7684Single doses of ONO-7684 or placebo orally under fed conditions |
| ONO-7684 Placebo Part A2 | Placebo comparator | Drug: ONO-7684 PlaceboSingle doses of ONO-7684 or placebo orally under fed conditions |
| ONO-7684 Part B1 | Experimental | Drug: ONO-7684Eligible subjects will receive multiple doses of ONO-7684 or placebo orally |
| ONO-7684 Placebo Part B1 | Placebo comparator | Drug: ONO-7684 PlaceboEligible subjects will receive multiple doses of ONO-7684 or placebo orally |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 18-55 years
- normotensive male volunteers, or female volunteers of non-childbearing potential (Part B only)
- body mass index 18.0-30.0 kg/m2
- deemed healthy on the basis of a clinical history, physical examination, ECG, vital signs, and laboratory tests of blood and urine
- registered with a General Practitioner (GP) in the UK
Key exclusion criteria (16 listed)
- Positive tests for hepatitis B \& C, HIV
- severe adverse reaction to any drug
- sensitivity to trial medication
- drug or alcohol abuse
- current smoker or use of nicotine containing products in the previous 6 months
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ONO-7684Single ascending doses for cohorts A1-A8 and multiple ascending doses cohorts B1-3 | Drug | ONO-7684 Part A1, ONO-7684 Part A2, ONO-7684 Part B1 |
| ONO-7684 PlaceboPlacebo comparator | Drug | ONO-7684 Placebo Part A1, ONO-7684 Placebo Part A2, ONO-7684 Placebo Part B1 |
Primary outcome
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)
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)
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.
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.
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.
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.
21 secondary outcomes
Pharmacokinetics (Cmax)
Time frame: 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
Pharmacokinetics (AUClast)
Time frame: 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
Pharmacokinetics (AUCt)
Time frame: 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
Pharmacokinetics (t1/2)
Time frame: Part A: Day 1 through Day 4. Part B: Day 14
Pharmacokinetics (CL/F)
Time frame: Day 1 through Day 4
Pharmacokinetics (Terminal Rate Constant)
Time frame: Day 1 through Day 4
Pharmacokinetics (Aet)
Time frame: Day 1 through Day 4
Pharmacokinetic (fe/F)
Time frame: Day 1 through Day 4
Pharmacokinetic (CLr)
Time frame: Day 1 through Day 4
Pharmacokinetic (Ctrough)
Time frame: Day 1 through Day 14
Pharmacokinetic (AUCtau)
Time frame: Day 14
Pharmacokinetic (CLSS/F)
Time frame: Day 14
Pharmacokinetic (VZ/F)
Time frame: 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
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
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
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Dec 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ONO-7684 in people with Venous Thromboembolism, run by Ono Pharmaceutical Co., Ltd. at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Dec 2019.