A SAD, MAD, and FE Study to Evaluate the Safety, Tolerability, and Pharmacokinetic Profile of FM101 in Healthy Volunteers

Study Overview
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Brief Summary
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This a double blind, randomized, placebo controlled, single and multiple ascending dose (SAD/MAD) study in healthy subjects. Safety evaluation will include adverse events (TEAEs), clinical laboratory values, vital signs, ECGs, and physical examinations.

Detailed Description
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This is a randomized, double-blind, placebo-controlled study in healthy volunteers designed to assess the safety, tolerability and PK of FM101. This study will consist of 3 parts: a SAD part, a single dose FE part and a MAD part. Each subject is to participate in only 1 part of the study.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Alternating Panel Single Ascending Dose, Sequential Multiple Ascending Dose, and Food Effect Study of FM101 in Healthy Male and Female Volunteers

Conditions
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Healthy Subjects

Intervention / Treatment
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* Drug: Single ascending doses of FM101
* Drug: Multiple ascending doses of FM101
* Drug: Food effects of FM101


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Gender: male or female Age: 18 - 50 years, inclusive, at screening Body mass index (BMI) : 18.0 - 32.0 kg/m2 (inclusive) Weight : ≥ 50 kg Status : healthy subjects At screening, females must be non-pregnant and non-lactating, or of non child-bearing potential (either surgically sterilized or physiologically incapable of becoming pregnant, or at least 1 year post menopausal [amenorrhea duration of 12 consecutive months); non-pregnancy will be confirmed for all females by a serum pregnancy test conducted at screening, and a urine pregnancy test at each admission and at follow-up. Female subjects of child-bearing potential, with a fertile male sexual partner, must agree to use adequate contraception from screening until 90 days after the follow up visit. Adequate contraception is defined as using hormonal contraceptives or an intrauterine device combined with at least 1 of the following forms of contraception: a diaphragm or cervical cap, or a condom. Also, total abstinence, in accordance with the lifestyle of the subject, is acceptable. Male subjects, if not surgically sterilized, must agree to use adequate contraception and not donate sperm from first admission to the clinical research center until 90 days after the follow-up visit. Adequate contraception for the male subject (and his female partner) is defined as using hormonal contraceptives or an intrauterine device combined with at least 1 of the following forms of contraception: a diaphragm or cervical cap, or a condom. Also, total abstinence, in accordance with the lifestyle of the subject is acceptable. All prescribed medication must have been stopped at least 14 days prior to (each) admission to the clinical research center. An exception is made for hormonal contraceptives, which may be used throughout the study. All over-the-counter medication, vitamin preparations and other food supplements, or herbal medications (eg, St. John's Wort) must have been stopped at least 7 days prior to (each) admission to the clinical research center. An exception is made for paracetamol, which is allowed up to admission to the clinical research center. Ability and willingness to abstain from alcohol, methylxanthine-containing beverages or food (coffee, tea, cola, chocolate, energy drinks), grapefruit (juice), and tobacco products from 48 hours prior to (each) admission to the clinical research center. Good physical and mental health on the basis of medical history, physical examination, clinical laboratory, ECG, and vital signs, as judged by the Investigator. Willing and able to sign the ICF. Exclusion Criteria: Employee of CRO or the Sponsor. History of relevant drug and/or food allergies. Using tobacco products within 60 days prior to (the first) drug administration. History of alcohol abuse or drug addiction (including soft drugs like cannabis products). Positive drug and alcohol screen (opiates, methadone, cocaine, amphetamines [including ecstasy], cannabinoids, barbiturates, benzodiazepines, gamma hydroxybutyric acid [GHB], tricyclic antidepressants, and alcohol) at screening and (each) admission to the clinical research center. Average intake of more than 24 units of alcohol per week (1 unit of alcohol equals approximately 250 mL of beer, 100 mL of wine, or 35 mL of spirits). Positive screen for hepatitis B surface antigen (HBsAg), anti hepatitis C virus (HCV) antibodies, or anti human immunodeficiency virus (HIV) 1 and 2 antibodies. Participation in a drug study within 60 days prior to (the first) drug administration in the current study. Participation in more than 3 other drug studies (for male subjects) / more than 2 other drug studies (for female subjects) in the 10 months prior to (the first) drug administration in the current study. Donation or loss of more than 100 mL of blood within 60 days prior to (the first) drug administration. Donation or loss of more than 1.5 liters of blood (for male subjects) / more than 1.0 liters of blood (for female subjects) in the 10 months prior to (the first) drug administration in the current study. Significant and/or acute illness within 5 days prior to (the first) drug administration that may impact safety assessments, in the opinion of the Investigator. Non-willingness to consume the high-fat breakfast (Part B only). Unsuitable veins for infusion or blood sampling.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo for SAD<br>Placebo comparator for SAD | Drug: Single ascending doses of FM101<br>* The study drug (FM101 and placebo comparator) will be administered orally as SAD doses<br>|
| Experimental: FM101 75 mg for SAD<br>Single ascending doses of FM101 | Drug: Single ascending doses of FM101<br>* The study drug (FM101 and placebo comparator) will be administered orally as SAD doses<br>|
| Experimental: FM101 150 mg for SAD<br>Single ascending doses of FM101 | Drug: Single ascending doses of FM101<br>* The study drug (FM101 and placebo comparator) will be administered orally as SAD doses<br>|
| Experimental: FM101 300 mg for SAD<br>Single ascending doses of FM101 | Drug: Single ascending doses of FM101<br>* The study drug (FM101 and placebo comparator) will be administered orally as SAD doses<br>|
| Experimental: FM101 600 mg for SAD<br>Single ascending doses of FM101 | Drug: Single ascending doses of FM101<br>* The study drug (FM101 and placebo comparator) will be administered orally as SAD doses<br>|
| Experimental: FM101 1200 mg for SAD<br>Single ascending doses of FM101 | Drug: Single ascending doses of FM101<br>* The study drug (FM101 and placebo comparator) will be administered orally as SAD doses<br>|
| Experimental: FM101 2400 mg for SAD<br>Single ascending doses of FM101 | Drug: Single ascending doses of FM101<br>* The study drug (FM101 and placebo comparator) will be administered orally as SAD doses<br>|
| Placebo Comparator: Placebo for MAD<br>Placebo comparator for MAD | Drug: Multiple ascending doses of FM101<br>* The study drug (FM101 and placebo comparator) will be administered orally as MAD doses<br>|
| Experimental: FM101 150 mg (QD) for MAD<br>Multiple ascending doses of FM101 | Drug: Multiple ascending doses of FM101<br>* The study drug (FM101 and placebo comparator) will be administered orally as MAD doses<br>|
| Experimental: FM101 450 mg (QD) for MAD<br>Multiple ascending doses of FM101 | Drug: Multiple ascending doses of FM101<br>* The study drug (FM101 and placebo comparator) will be administered orally as MAD doses<br>|
| Experimental: FM101 600 mg (BID) for MAD<br>Multiple ascending doses of FM101 | Drug: Multiple ascending doses of FM101<br>* The study drug (FM101 and placebo comparator) will be administered orally as MAD doses<br>|
| Experimental: FM101 300 mg under fasted condition for FE<br>Food Effect of FM101 | Drug: Food effects of FM101<br>* The study drug (FM101) will be administered orally under fasted condition and fed condition.<br>|
| Experimental: FM101 300 mg under fed condition for FE<br>Food Effect of FM101 | Drug: Food effects of FM101<br>* The study drug (FM101) will be administered orally under fasted condition and fed condition.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the safety and tolerability of FM101 after SAD and MAD doses to healthy volunteers by assessing the number, severity, and type of TEAEs. | The number of TEAEs (frequency of occurrence, number of subjects experiencing the event) | SAD [Day 1 through Day 7], MAD [Day 1 through Day 10] | 
| To evaluate the change in clinical laboratory values from the baseline after SAD and MAD doses. | The number of abnormalities with clinical significance (frequency of occurrence, number of subjects experiencing the event) | SAD [Day 1 through Day 7], MAD [Day 1 through Day 10] | 
| To evaluate the change in vital signs from the baseline after SAD and MAD doses. | The number of abnormalities with clinical significance (frequency of occurrence, number of subjects experiencing the event) | SAD [Day 1 through Day 7], MAD [Day 1 through Day 10] | 
| To evaluate the change in electrocardiograms (ECGs) after SAD and MAD doses. | The number of abnormalities with clinical significance (frequency of occurrence, number of subjects experiencing the event). | SAD [Day 1 through Day 7], MAD [Day 1 through Day 10] | 
| To evaluate the change in physical examinations after SAD and MAD doses. | The number of abnormalities with clinical significance (frequency of occurrence, number of subjects experiencing the event). | SAD [Day 1 through Day 7], MAD [Day 1 through Day 10] | 
| To assess maximum observed plasma concentration (Cmax) following SAD and MAD doses | Cmax of FM101 in plasma will be calculated as applicable: SAD phase - cohort 1 to 6 , MAD phase - cohort 2 | SAD phase - Day 1 at pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 15, 24, 36, 48, and 72 hours. MAD phase - Day 1 at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after the first dose. Day 3 to Day 7 at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours. | 
| To assess area under plasma concentration-time curve from hour 0 to last sample following SAD and MAD doses | AUClast of FM101 in plasma will be calculated as applicable: SAD phase - cohort 1 to 6 , MAD phase - cohort 2 | SAD phase - Day 1 at pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 15, 24, 36, 48, and 72 hours. MAD phase - Day 1 at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after the first dose. Day 3 to Day 7 at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours. | 
| To assess area under plasma concentration-time curve from hour 0 to infinity following SAD and MAD doses | AUCinf of FM101 in plasma will be calculated as applicable: SAD phase - cohort 1 to 6 , MAD phase - cohort 2 | SAD phase - Day 1 at pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 15, 24, 36, 48, and 72 hours. MAD phase - Day 1 at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after the first dose. Day 3 to Day 7 at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours. | 
| To assess time to reach the maximum concentration in plasma (Tmax) following SAD and MAD doses | Tmax of FM101 in plasma will be calculated as applicable: SAD phase - cohort 1 to 6 , MAD phase - cohort 2 | SAD phase - Day 1 at pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 15, 24, 36, 48, and 72 hours. MAD phase - Day 1 at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after the first dose. Day 3 to Day 7 at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours. | 
| To assess terminal elimination rate constant (Kel) following SAD and MAD doses | Kel of FM101 in plasma will be calculated as applicable: SAD phase - cohort 1 to 6 , MAD phase - cohort 2 | SAD phase - Day 1 at pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 15, 24, 36, 48, and 72 hours. MAD phase - Day 1 at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after the first dose. Day 3 to Day 7 at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours. | 
| To assess terminal half-life (t1/2) following SAD and MAD doses | t1/2 of FM101 in plasma will be calculated as applicable: SAD phase - cohort 1 to 6 , MAD phase - cohort 2 | SAD phase - Day 1 at pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 15, 24, 36, 48, and 72 hours. MAD phase - Day 1 at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after the first dose. Day 3 to Day 7 at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the effect of food on the plasma Cmax of FM101 after a single dose | Cmax of FM101 under fasted and fed conditions will be calculated after a single dose. | Day 1 pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 15, 24, 36, 48, and 72 hours post-dose. | 
| To evaluate the effect of food on the plasma AUClast of FM101 after a single dose | AUClast of FM101 under fasted and fed conditions will be calculated after a single dose. | Day 1 pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 15, 24, 36, 48, and 72 hours post-dose. | 
| To evaluate the effect of food on the plasma AUCinf of FM101 after a single dose | AUCinf of FM101 under fasted and fed conditions will be calculated after a single dose. | Day 1 pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 15, 24, 36, 48, and 72 hours post-dose. | 
| To evaluate the effect of food on the plasma Tmax of FM101 after a single dose | Tmax of FM101 under fasted and fed conditions will be calculated after a single dose. | Day 1 pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 15, 24, 36, 48, and 72 hours post-dose. | 
| To evaluate the effect of food on the plasma Kel of FM101 after a single dose | Kel of FM101 under fasted and fed conditions will be calculated after a single dose. | Day 1 pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 15, 24, 36, 48, and 72 hours post-dose. | 
| To evaluate the effect of food on the plasma t1/2 of FM101 after a single dose | t1/2 of FM101 under fasted and fed conditions will be calculated after a single dose. | Day 1 pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 15, 24, 36, 48, and 72 hours post-dose. |