A phase I trial to study the effect of food on orally dosed IMG-7289 (Bomedemstat) in healthy adult volunteers
- Conditions
- Acute myeloid leukaemia (AML)Myelodysplastic syndrome (MDS)Cancer - Leukaemia - Acute leukaemiaBlood - Haematological diseasesCancer - Other cancer types
- Registration Number
- ACTRN12621001349831
- Lead Sponsor
- Avance Clinical
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 17
Healthy volunteers will be included in this study if they satisfy all the following criteria:
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.
3. 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.
4. Be nonsmokers (including tobacco, e-cigarettes, marijuana or other nicotine containing product) for at least 3 months prior to first study drug administration and have a negative result of cotinine test at screening and on Day -1 for each confinement period.
5. No prior history of chronic alcohol abuse or excessive alcohol intake, at the discretion of the Principal Investigator (PI), within 12 weeks prior to screening, and negative alcohol test results.
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 for each confinement period. 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 clinically significant abnormalities at screening 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 90 to 160 mmHg and diastolic blood pressure in the range of 50 to 95 mmHg after 5 minutes in supine position;
c. Heart rate in the range of 45 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 electrocardiogram (ECG) within normal range 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.
The above assessments may be repeated once, if abnormal values were recorded in the first instance, at the discretion of the PI.
9. Female participants must:
a. Be of nonchildbearing potential
b. If of childbearing potential, must have a negative pregnancy test at screening (blood test) and before the first study drug administration (Day -1 urine test). They must agree not to attempt to become pregnant, must not donate ova, and must use a highly effective contraceptive method from signing the consent form until at least 30 days after the last dose of study drug.
c. Must not be breast-feeding.
10. Male participants, if not surgically sterilised, must be willing not to donate sperm and, if engaging in sexual intercourse with a female partner who could become pregnant, must be willing to use a condom in addition to having the female partner use a highly effective contraceptive method from signing the consent form until at least 90 days after the last dose of study drug.
11. Have suitable venous access for blood sampling.
12. Be willing and able to comply with all study assessments and adhere to the protocol schedule and restrictions.
Healthy volunteers will be excluded from this study if there is evidence of any of the following at screening or after check in prior to dose administration on Day 1 (clinical and laboratory assessments may be repeated once, at the discretion of the PI, in the case of abnormal findings in the first instance):
1. History or presence of significant cardiovascular, pulmonary, hepatic, renal, haematological, gastrointestinal, endocrine, immunologic, dermatologic or neurological disease, including any acute illness or surgery within the past 3 months determined by the PI to be clinically relevant.
2. Current infection that requires antibiotic, antifungal, antiparasitic or antiviral medications.
3. Any history of malignant disease in the last 5 years (except basal cell skin cancer or squamous cell skin cancer with history of curative treatment and no recurrence for more than 1 year prior to screening).
4. Presence of clinically relevant immunosuppression from, but not limited to, immunodeficiency conditions such as common variable hypogammaglobulinemia.
5. Use of or plans to use systemic immunosuppressive (e.g., corticosteroids, methotrexate, azathioprine, cyclosporine) or immunomodulating medications (e.g., interferon) during the study or within 4 months prior to the first study drug administration.
6. Liver function test results (i.e., aspartate aminotransferase [AST], alanine aminotransferase [ALT], and gammaglutamyl transferase [GGT]) and total bilirubin elevated greater than or equal to 1.5-fold above the normal limits.
7. Abnormal renal function tests, indicated by calculated creatinine clearance less than 80 mL/min, and serum creatinine greater than 1.5-fold of the normal range, respectively.
8. History of bleeding diathesis, thrombocytopenia or other clotting or coagulation disorder.
9. Platelets below the lower limit of normal (150 x 109/L).
10. Family history of long QT syndrome or of unexplained sudden death in a first-degree relative under 50 years of age.
11. Positive test results for active human immunodeficiency virus (HIV-1 or HIV-2), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibodies.
12. Presence or having sequelae of gastrointestinal, liver, kidney, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs.
13. Use of any prescription medication within 14 days or 7 half-lives of the medication (whichever is longer) prior to the first study drug administration (except hormonal contraceptives associated with inhibition of ovulation and other medication deemed non-clinically relevant by the PI in consultation with Imago BioSciences).
14. Use of over-the-counter medication excluding routine vitamins and herbal supplements (paracetamol less than 2 grams/day is acceptable) but including mega dose vitamin therapy and St John’s Wort within 7 days of first dosing and throughout the study, unless agreed as non-clinically relevant by the PI.
15. Consumption of caffeine or alcohol, or any products containing grapefruit, Seville orange, star fruit or pomegranate within 48 hours prior to the first IMG-7289 dose administration on Day 1 (consumption is also not permitted within 48 hours of Day 1 for each period).
16. Demonstrated clinically significant (required intervention, e.g., emergency room visit, epinephrine administration) allergic reactions (e.g., food, drug, or atopic reactions, asthmatic episodes) which, in the opinion of the PI, would inter
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To evaluate the effect of food on the pharmacokinetics of two formulations of IMG-7289 when administered orally at a dose of 50 mg either after a high fat/calorie meal or after an overnight fast.<br>The parameters assessed for the pharmacokinetics endpoints include Maximum observed concentration (Cmax), Time to Cmax (Tmax), Area under the concentration-time curve (AUC0-tlast; AUC0-inf; AUC0-24h; AUC0-48h), Terminal elimination half-life (t1/2), Terminal elimination rate constant, Apparent total body clearance, Apparent volume of distribution<br>[ Day 1 on each of the four study periods (within 45 minutes before dose administration and at 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72, 120, 168, 192, and 240 hours post-dose.]
- Secondary Outcome Measures
Name Time Method To assess the safety and tolerability of two formulations of IMG-7289 administered in a fasted and fed state<br>The parameters assessed to monitor this outcome include incidence, severity and relationship of adverse events, change in physical examination findings, body weight measured with a body scale in kg, body mass index (BMI), vital signs, including blood pressure measured with a sphygmomanometer, pulse rate and respiratory rate measured by visual and physical examination, body temperature measured by oral or typmpanic thermometer, electrocardiogram (ECG) used to measure electrical activity of the heart, and clinical laboratory assessments performed on blood and urine samples.[ From time of first dose to the end of study visit (all participants will be closely monitored, asked how they are feeling, and will spend 4 nights in clinic followed by 4 follow-up visits during each of the four study periods.)]