Single Ascending Dose Trial Investigating Safety, Tolerability and Pharmacokinetics of BDM-2 in Healthy Male Subjects.

Study Overview
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Brief Summary
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This is a first-in-human (FIH), double-blind, placebo-controlled, randomized trial in healthy adult male subjects, to evaluate the safety, tolerability and pharmacokinetics (PK) of single ascending oral doses of BDM-2. The effect of food on the PK of a single dose of BDM-2 will also be evaluated.

Detailed Description
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The Sponsor HIVIH is developing a new antiretroviral medicine, BDM-2, for the potential treatment of Human Immunodeficiency Virus (HIV). The study will investigate the safety, tolerability and pharmacokinetics (PK) (how well the medicine is taken up by the body) of single doses of the test medicine given by mouth, in healthy male volunteers. The effect of food on the PK of the test medicine will also be assessed. This is the first time the medicine will be dosed in humans. Over 6 study periods, ascending (increasing) doses of the test medicine or placebo (dummy drug) will be given to 16 healthy male volunteers in the fasted state. Alternately dosed to two groups each made up of 8 volunteers. After each dose volunteers will remain in the clinical unit for 48 hours for blood samples to be taken and safety assessments to be performed. To investigate the effect of food, it is planned that in Period 7 the medicine will be administered in the fed state. On the 7th study period one of the doses administered in a previous period will be administered under fed conditions (with food). Each volunteer will receive 3 or 4 single doses of test medicine or placebo.

Official Title
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A Single Ascending Dose Trial Investigating the Safety, Tolerability and Pharmacokinetics of Orally Administered BDM-2 in Healthy Male Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: BDM-2 in Bottle (50 mg - 3600 mg); oral suspension


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male aged between 18 and 55 years at screening, inclusive. Body Mass Index (BMI) 18.0-32.0 kg/m2 at screening, inclusive. Good physical and mental health as established by medical history, physical examination, respiratory rate, electrocardiogram (ECG) and vital signs (including body temperature) recording, and results of biochemistry, coagulation, hematology and urinalysis tests during screening as judged by the investigator. Non-smoker/non-user of nicotine containing products for at least 3 months prior to screening, to be confirmed by a urine cotinine dipstick test at screening and on Day -1 of the first session. Availability and willingness to complete the trial and follow the instructions of the investigator or trial-site personnel. Willing and able to adhere to the prohibitions and restrictions specified in the protocol Easy venous accessibility. Must have signed an Informed Consent Form (ICF) prior to screening, indicating that he understands the purpose of, and procedures required for the trial, and is willing to participate in the trial. Must agree to provide a blood sample for DNA research. Subject who is heterosexually active with a woman of childbearing potential must agree to use 2 effective methods of birth control (i.e., male condom with either female intrauterine device, diaphragm, cervical cap or hormone-based contraceptive), during the trial and for at least 90 days after receiving the last dose of trial medication. If the female sexual partner is postmenopausal for at least 2 years, or is surgically sterile (has had a total hysterectomy, bilateral oophorectomy, or bilateral tubal ligation/bilateral tubal clips without reversal operation), or otherwise is incapable of becoming pregnant, the birth control methods mentioned are not applicable, however, subjects should use a condom during the trial and for at least 90 days after receiving the last dose of trial medication to prevent unintended exposure via the ejaculate. Subjects who had vasectomy and have a female partner of childbearing potential must use a male condom during the trial and for at least 90 days after receiving the last dose of trial medication. Note: A male and female condom should not be used together due to risk of breakage or damage caused by latex friction. Note: Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the trial medication (during the trial and for at least 90 days after receiving the last dose of trial medication). The reliability of sexual abstinence needs to be evaluated in relation to the duration of the trial and the preferred and usual lifestyle of the subject. Note: Subjects will be instructed that if their partner becomes pregnant during the trial this should be reported to the investigator. The investigator should also be notified of pregnancy occurring during the trial but confirmed after completion of the trial. In the event that a subject's partner is subsequently found to be pregnant after the subject is included in the trial, then consent will be sought from the partner and, if granted, any pregnancy will be followed and the status of mother and/or child will be reported to the sponsor after delivery. Must agree not to donate sperm during the trial and for at least 90 days after receiving the last dose of trial medication. Exclusion Criteria: History of or current clinically significant medical illness including (but not limited to) gastrointestinal, cardiovascular, neurologic, psychiatric, metabolic, endocrinologic, genitourinary, renal, hepatic, respiratory, inflammatory, neoplastic, or infectious disease, or any other illness that the investigator considers should exclude the subject or that could interfere with the interpretation of the trial results. Clinically significant abnormalities of hematology or biochemistry (out of range values should be considered as to their significance and the subject not included if the value is considered to be detrimental). This includes but is not limited to liver function tests. Subjects with Gilbert's syndrome. Clinically significant presence or history of allergy or intolerance (including lactose), or presence or history of clinically significant allergy requiring treatment, as judged by the investigator (hay fever is allowed unless it is active). Positive serology for hepatitis A virus (HAV) immunoglobulin M (IgM), hepatitis B virus surface antigen (HBsAg), anti-hepatitis C virus antibodies (anti-HCV-AB), or anti HIV antibodies 1+2 (anti-HIV-AB 1+2) at screening. History of alcohol or drug abuse within the last 2 years before screening or positive test result(s) for alcohol and/or drugs of abuse at screening or on Day -1 of first session. Regular alcohol consumption >21 units per week (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine). Surgery of gastro-intestinal tract that might interfere with absorption (subjects who have had cholecystectomy may be included). Subject has currently significant and active diarrhea, nausea, or constipation that in the investigator's opinion could influence drug absorption or bioavailability. Intake of any disallowed therapies before the first dose of trial medication (on Day 1 of the first session). Donation of blood or blood products or substantial loss of blood (more than 500 mL) within 3 months before first dose of trial medication (on Day 1 of the first session) or the intention to donate blood or blood products during the trial Major surgery, fracture, or prolonged immobilization (more than 2 weeks) within 3 months preceding screening, or surgery has been planned during the time the subject is expected to participate in the trial. Unable to swallow solid, oral dosage forms (multiple capsules) whole with the aid of water (subjects may not chew, divide, dissolve, or crush the trial medication). Plans to father a child while enrolled in the trial or within 90 days after receiving the last dose of trial medication. History of hypersensitivity or idiosyncrasy to any of the components of the investigational drug. Participation in a clinical trial within 3 months before first dose of trial medication (on Day 1 of the first session). Participation in a trial of an investigational product or an experimental medical device within 3 months or within a period less than 5 times the drug's half-life, whichever is longer, prior to the first dose (on Day 1 of the first session) or during this trial. Trial site employee or immediate family members of a trial site or sponsor employee. Have previously been enrolled in this trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

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: Parallel Assignment
Interventional Model Description: In Sessions I to VI, 6 single, orally administered ascending doses of BDM-2 or placebo will be investigated, alternately dosed in 2 cohorts of 8 healthy male subjects each (Cohorts A and B). For each dose, 6 subjects will receive active treatment and 2 subjects will receive placebo. Subjects will be randomized in such a way that for each dose different subjects receive placebo. In Sessions I to VI, doses are planned to be administered under fasted conditions.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A<br>Ascending doses of BDM-2 in Bottle (50 mg - 3600 mg); oral suspension or placebo will be orally administered and will be investigated, alternately dosed in Cohort A of 8 healthy male subjects under fasted conditions. For each dose, 6 subjects will receive active treatment and 2 subjects will receive placebo. Subjects will be randomized in such a way that for each dose different subjects receive placebo. The last session for the subjects in Cohort A will be under fed conditions where the same treatment allocation as in the session of the selected dose (administered under fasted conditions) will be used. | Drug: BDM-2 in Bottle (50 mg - 3600 mg); oral suspension<br>* BDM-2 in bottle will be reconstituted with a 100 mL vehicle (0.2% Sodium Dodecyl Sulfate and water) to achieve a suspension for oral administration.<br>|
| Experimental: Cohort B<br>Ascending doses of BDM-2 in Bottle (50 mg - 3600 mg); oral suspension or placebo will be orally administered and will be investigated, alternately dosed in Cohort B of 8 healthy male subjects under fasted conditions. For each dose, 6 subjects will receive active treatment and 2 subjects will receive placebo. Subjects will be randomized in such a way that for each dose different subjects receive placebo. | Drug: BDM-2 in Bottle (50 mg - 3600 mg); oral suspension<br>* BDM-2 in bottle will be reconstituted with a 100 mL vehicle (0.2% Sodium Dodecyl Sulfate and water) to achieve a suspension for oral administration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Treatment Related Adverse Event, Including Abnormal Laboratory Events | All AEs, including clinical laboratory, vitals signs, body temperature, respiratory rate, physical examinations and ECGs will be analyzed in all subjects receiving BDM-2. | up to 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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safety, tolerability, pharmacokinetics