None listed
Conditions
Brief summary
The present study is a first-in-human (FIH) study aimed to investigate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of M102 in healthy participants and aims to investigate both single and multiple doses of M102, as well as investigate the impact of food on the PK profile of M102. Up to 80 participants are planned to be randomized to the study. There are two cohorts- Part A (SAD) and Part B (MAD) cohorts. Total duration of study participation for each participant is up to approximately 36 days for Part A and up to approximately 50 days for Part B. In Part A and Part B, sequential cohorts will be exposed to increasing doses of M102 in order to identify an optimal therapeutic dose for future studies. M102 is an oral drug that may be able to reverse several disease pathways that cause Amyotrophic Lateral Sclerosis (ALS), a fatal, incurable disease of the nervous system. Testing the safety of taking the drug and the amount of drug in the body will help decide what dose to study in patients.
Interventions
This is a double-blind, placebo-controlled, ascending dose, multi-cohort trial. The study will be conducted in 2 phases: a single ascending dose (SAD) phase Part A and a multiple ascending dose (MAD) phase Part B in healthy volunteers.
In Part A, participants will receive a single-dose of either study drug (M102) or placebo. In Part B, participants will receive daily doses of M102 or placebo for 14 days. The first Part B cohort (Cohort 1) will be dosed for 7 days. In Part A and Part B, sequent
This is a double-blind, placebo-controlled, ascending dose, multi-cohort trial. The study will be conducted in 2 phases: a single ascending dose (SAD) phase Part A and a multiple ascending dose (MAD) phase Part B in healthy volunteers. In Part A, participants will receive a single-dose of either study drug (M102) or placebo. In Part B, participants will receive daily doses of M102 or placebo for 14 days. The first Part B cohort (Cohort 1) will be dosed for 7 days. In Part A and Part B, sequential cohorts will be exposed to increasing doses of M102 in order to identify an optimal therapeutic dose for future studies. Part A- This consists of 6 cohorts where participants will receive a single-dose of either study drug (M102) or placebo on Day 1. The planned doses of IP from A1 to A5 will be 70mg, 140mg, 280mg, 560mg and 1120 mg which will be conducted in fasted state (no food for 8 hours prior to dosing). Based upon review of the safety and PK data from Part A, a cohort (1 of Cohort A1 to A5) will be invited to return for a crossover food effect study (Cohort A6). All cohorts will consent to this adaptive design upon study enrollment. The food effect study (Cohort A6 at target therapeutic dose) may be run concurrently with other cohorts. Please note: Food effect cohort participants will receive the same treatment they previously received during their initial dosing The washout period for the crossover food effect cohort will be at least 7 days between the two treatment periods. Part B- This part consists of 5 cohorts where participants will receive either study drug or placebo on a daily basis for 7 days (cohort 1) or 14 days (cohort 2-5). The planned dose of IP fromB1 to B3 are as follows- 140mg, 280 and 560mg. Doses for B4 and B5 will be based on the review of safety, tolerability and pharmacokinetic (PK) of the previous cohorts. Following ongoing review of safety and available PK data from Part A, as well as modeling of expected repeated-dose steady state exposures with daily dosing, the multiple ascending dose Part B will commence in a minimum of 3 cohorts and up to 5 cohorts. Part B may commence prior to completion of all cohorts in Part A. Adherence to the intervention will be ensured by participant confinement during the dosing period.
Sponsors
Aclipse One, Inc.
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver)
Eligibility
Sex/Gender
All
Age
18 Years to 64 Years
Healthy volunteers
Yes
Inclusion criteria
1. Aged 18 to 64 years (inclusive) at the time of informed consent. 2. At the discretion of the PI or designee, in good general health, with no significant medical history, and have no clinically significant abnormalities on physical examination at Screening and/or before the first administration of IP. 3. BMI between more than equal to 18.0 and less than equal to 32.0 kg/m2 and weight more than equal to 50 kg. 4. Non-smokers and casual smokers who smoke less than equal to 5 cigarettes or equivalent (eg, cigars, vaping, nicotine patches) per week can be included in the study at the discretion of the PI or designee, provided they can abstain from smoking from time of Screening until EOS. 5. Clinical laboratory values within normal range as specified by the testing laboratory, unless deemed not clinically significant by the PI or designee. 6. Not pregnant or breastfeeding, or willing to cease breastfeeding. 7. Woman of childbearing potential or fertile man agrees to use an acceptable method of contraception from the start of Screening until 90 days after the last dose of IP. Notes: a. Males must be congenitally sterile (with supportive medical documentation), or surgically sterile (> 30 days since vasectomy with no viable sperm) or, if engaged in sexual relations with a WOCBP, must agree to use an acceptable contraceptive method. b. Females or males with same-sex partners (abstinence from penile-vaginal intercourse) or who are abstinent from heterosexual intercourse are not required to use contraception when this is their preferred and usual lifestyle. c. Males must not donate sperm from the first dose of IP until at least 90 days after the last dose of IP. d. Females are required to abstain from ova/egg donation during the study 8. For Cohort A6 only, be willing to consume a standardized, high-fat, high-calorie meal on the morning of dosing. 9. Participant agrees to avoid cruciferous vegetables (ie, broccoli, cauliflower, brussels sprouts, artichoke, kale, Chinese cabbage, radish, wasabi, horseradish, turnip) from at least 14 days prior to first dose of the study drug until 7 days post-final dose. 10. Participant is normotensive as defined by systolic blood pressure (BP) less than equal to 140 mmHg and diastolic less than equal to 90 mmHg. 11. Able and willing to attend the study site for the full confinement period. 12. Able and willing to provide written informed consent after the nature of the study has been explained and prior to the commencement of any study procedures.
Exclusion criteria
1. Underlying physical or psychological medical condition that, in the opinion of the PI or designee, would make the participant unlikely to comply with the protocol or complete the study per-protocol. 2. Recent history (within 12 months of Screening) of moderate to severe depressive disorder. 3. Blood or plasma donation or had significant blood loss (more than equal to 500 mL) within 30 days prior to the first administration of IP. 4. Fever (body temperature >38°C) or symptomatic viral or bacterial infection within 2 weeks prior to Screening or Day -1. 5. Poor pill swallowing ability 6. Positive test for hepatitis C antibody (HCV), hepatitis B surface antigen (HBsAg), human immunodeficiency virus (HIV)-1/ -2 antibody. 7. Infections requiring parenteral antibiotics within 6 months prior to Screening. 8. History of life-threatening infection (eg, meningitis). 9. Vaccination with a live vaccine within 4 weeks prior to the first administration of IP. 10. History of severe allergic or anaphylactic reactions, or sensitivity to the IP or its constituents. 11. History of malignancy, except for non-melanoma skin cancer, excised more than 2 years ago and cervical intraepithelial neoplasia that has been successfully cured more than 5 years prior to Screening. 12. Abnormal ECG findings at Screening or Day -1 that are considered by the PI or designee to be clinically significant. The following abnormalities should be excluded: a. Participant has left ventricular hypertrophy defined as the combination of the following ECG criteria (both i. and ii. must be met): i. Voltage criteria (both criteria must be met): - S in V1 + R in V5 or V6 (whichever is larger) more than equal to 35 mm; and - R in aVL more than equal to 11 mm. ii. Repolarization abnormalities (at least one criterion needs to be met): - At least 1 mm ST depression (horizontal or down-sloping); or - Abnormal T wave inversions. b. Participant has other significant ECG abnormalities that might interfere with ECG analysis including evidence of a previous myocardial infarction, flat T waves (particularly in the inferior leads) or more than minor non-specific ST-T wave changes or: i. QRS > 120 milliseconds (msec). ii. QT interval corrected using Fridericia’s formula (QTcF) more than equal to 450 msec (men) and more than equal to 460 msec women). iii. PR interval > 220 msec. iv. Heart rate < 45 beats per minute (bpm) or > 90 bpm. v. Complete right bundle branch block or left bundle branch block. vi. History of Congenital long QT syndrome 13. Participant is regularly using any restricted mediations including 5HT3 antagonists, antihypertensive medications, vasodilators, drugs that may prolong QTc interval, drugs known to modulate CYP2C8 or CYP3A4, or known substrates of CYP1A2. 14. Participant exhibits any signs of dementia or cognitive impairment. 15. Alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) > 1.5 × upper limit of normal (ULN) at Screening. Repeat testing at Screening is acceptable for out-of-range values following approval by the PI or designee. 16. Positive toxicology screening panel (urine test including qualitative identification of tetrahydrocannabinol (THC), cocaine, amphetamines, barbiturates, benzodiazepines, opiates, methadone, methamphetamines, methylenedioxymethamphetamine (MDMA), and phencyclidine (PCP)], or alcohol breath test. 17. History of substance abuse or dependency or history of recreational intravenous (IV) drug use over the last 2 years (by self-declaration). 18. Regular alcohol consumption defined as > 10 standard drinks per week (where 1 standard drink equal to 360 mL of beer, 45 mL of 40% spirit or a 150 mL glass of wine) or > 4 standard drinks on any single day. 19. Unwilling to abstain from alcohol from 48 hours prior to admission to the study site until EOS. 20. Use of any investigational medical device or investigational drug within 30 days or 5 half-lives of the investigational drug (whichever is longer) prior to the first administration of the IP. 21. Use of (or anticipated use of) any prescription drugs (other than hormone replacement therapy or hormonal contraception; oral contraceptive pills, long-acting implantable hormones, injectable hormones, a vaginal ring, or an intrauterine device [IUD]), over-the-counter medication, herbal remedies, supplements or vitamins within 7 days prior to the first administration of IP (or 14 days for remedies or supplements known to modulate CYP3A4 such as St John’s Wort) and during the course of the study without prior approval of the PI and MM. Simple analgesia (paracetamol, nonsteroidal anti-inflammatory drug [NSAID]) may be permitted at the discretion of the PI. 22. Unwilling to refrain from strenuous exercise (including weightlifting) from 5 days prior to admission to the study site until EOS. 23. Anything that the PI considers would jeopardize the safety of the participant, prevent complete participation in the study, or compromise interpretation of study data.
Outcome results
None listed