An Open-Label, Phase 1 Study to Characterize the Effects of a Moderate CYP3A4 and P-glycoprotein Inhibitor on the Pharmacokinetics of Bomedemstat (IMG-7289) in Healthy Participants
- Conditions
- CancerCancer - MyelomaBlood - Haematological diseases
- Registration Number
- ACTRN12623001006639
- Lead Sponsor
- Imago BioSciences, Inc., a subsidiary of Merck & Co., Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 24
1.Must have given written informed consent before any study related activities are carried out and must be able to understand the full nature and purpose of the trial, including possible risks and adverse effects.
2.Adult males and females, 18 to 65 years of age (inclusive) at Screening Visit.
3.Body mass index (BMI) greater than or equal to 18.0 and less than or equal to 32.0 kg/m2, with a body weight greater than or equal to 55 and less than or equal to 100 kg at Screening Visit.
4.Be non-smokers (including tobacco, e-cigarettes or other nicotine containing products, and marijuana) for at least 1 month prior to first study drug administration and have a negative result of cotinine test at screening and on Day -1. In the event the cotinine test is positive, the test may be repeated once (at the discretion of the PI) to confirm eligibility.
5.No prior history of chronic alcohol abuse or excessive alcohol intake, at the discretion of the PI, within 12 weeks prior to screening. No alcohol is to be consumed for at least 48 hours prior to admission, with negative alcohol test results (at screening and on Day -1). In the event the alcohol breath test is positive, the test may be repeated once (at the discretion of the PI) to confirm eligibility. Excessive alcohol intake is defined as regular consumption of >12 standard units of alcohol per week, or more than 4 standard drinks on >3 days per week, where 1 standard drink is 10 g of pure alcohol and is equivalent to 285 mL beer [4.9% Alc./Vol], 100 mL wine [12% Alc./Vol], 30 mL spirit [40% Alc./Vol]).
6.No prior history of substance abuse or drug addiction within 12 months prior to first study drug administration and negative urine drug screen results at screening and on Day -1. In the event the urinary drug test is positive, the test may be repeated once (at the discretion of the PI) to confirm eligibility.
7.No prior history of relevant drug hypersensitivity.
8.Medically healthy (in the opinion of the PI) as determined by pre-study medical history and without CS abnormalities at screening, and after check-in on Day -1, and prior to first dose administration on Day 1, including:
a.Physical examination without any clinically relevant findings;
b.Systolic blood pressure in the range of 100 to 160 mmHg and diastolic blood pressure in the range of 50 to 95 mmHg after 5 minutes in supine position;
c.Pulse rate (PR) in the range of 50 to 100 beats/minute after 5 minutes rest in supine position;
d.Body temperature (tympanic), between 35.5°C and 37.7°C;
e.A 12-lead ECG within normal range (QTcF males less than or equal to 450 ms; QTcF females less than or equal to 470 ms) or with abnormalities that are not hazardous to the participant according to the opinion of the PI;
f.No clinically relevant findings in clinical laboratory blood and urinalysis tests as judged by the PI;
g.ALT/AST less than or equal to 1.5 ULN, total bilirubin less than or equal to 1.5 x ULN and/or creatinine clearance greater than or equal to 80mL/min (calculated using Cockcroft & Gault formula).
NOTE: Laboratory results obtained during screening and prior to first dose administration on Day 1 should be used to determine eligibility criteria. In situations where laboratory results, vitals or ECGs are outside the permitted range, the Investigator may retest the participant once and the subsequent within range screening result may be used to determine the participant’s eligibility.
9.Participants wi
1.Is pregnant or nursing.
2.Has an active or prior malignancy.
Exception: Participants who has been disease-free for 1 year, or a participant with a history of a completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.
3.Has thrombocytopenia, neutropenia, or anaemia, i.e., not within the normal range based on local lab references with a single repeat and minor aberrations allowable at the discretion of the PI, and any prior history of myeloid malignancies, including MDS.
4.Has had major surgery (in the opinion of the Investigator) within 3 months prior to enrollment.
5.Is unwilling to exclude grapefruit, grapefruit juice or products that contain grapefruit, star fruit, pomegranate, pomelo, tangelo or Seville orange-containing products from the diet and all foods that contain those fruits from time of enrolment until discharge from the clinical unit.
6.Has cardiovascular impairment, history of congestive heart failure greater than New York Heart Association Class II, arterial hypertension, unstable angina, myocardial infarction, or stroke within 6 months prior to the planned first dose of bomedemstat; or ventricular cardiac arrhythmia requiring medical treatment.
7.Participants taking medications that are known potent or moderate inducers or inhibitors of CYP3A4 (including St. John’s Wort).
8.Blood or plasma donation of >100 mL during the 4 weeks prior to Day -1.
9.Participation in another clinical trial of an investigational molecule (or medical device) within 30 days (or 5 half-lives of the drug, whichever is longer) prior to the start of IP administration on Day 1 (or within 6 months or 5 half-lives, whichever is longer, prior to the start of IP administration on Day 1 if the investigational drug was an immunosuppressive biologic).
10.Received treatment with immune-suppressive or immune-modulative medication (including topical, systemic and inhalant corticosteroids) or have received immunoglobulins and/or blood products within 4 months prior to the administration of the first dose of IP.
11.Exposure to any prescription medications (small molecules), topically or systemically administered over-the-counter drugs, dietary supplements, or herbal remedies (with the exception of aspirin) within 14 days or 5 half-lives (if known), (whichever is longer) prior to the start of IP administration on Day 1.
12.Has an active infection or recent history (<30 days before study drug administration) requiring systemic treatment.
13.Is immunocompromised (in the opinion of the Investigator), including participants with known HIV infection.
14.Has known hypersensitivity to any of the components of the IP.
15.Is unable to take oral medications, has a history of surgery that in the opinion of the PI would interfere with the administration or absorption of oral medication, has malabsorption syndrome or any other uncontrolled gastrointestinal condition (e.g., nausea, diarrhoea or vomiting) that might impair the bioavailability of IP.
16.Has an uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, or psychiatric illness that would limit compliance with study requirements. At discretion of the PI, participants with any history of depression or suicidal ideation will be excluded and at a minimum, participants with a prior history should have stable mental state off medications for >6 months.
17.A history of bleeding (i.e., hemoptysis, hematuria, g
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method