First-time-in-man, to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BP1.5375

Study Overview
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Brief Summary
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Phase I Single Ascending Dose (Part 1), phase IIa Proof Of Concept (Part 2)

Detailed Description
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This is a single center, Double-blind, placebo controlled, randomized study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of BP1.5375 after single oral administrations ranging in healthy male subjects (Part 1) followed by the assessment of the effect of 3 single different BP1.5375 oral doses on polysomnography in comparison to 50 mg diphenhydramine and placebo in healthy male subjects (Part 2).

Official Title
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Double-blind, Placebo Controlled, Randomized Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BP1.5375 After Single Oral Administrations Ranging From 0.5 mg to 100 mg in Healthy Male Subjects (Part 1) Followed by the Assessment of the Effect of 3 Single Different BP1.5375 Oral Doses on Polysomnography in Comparison to 50 mg Diphenhydramine and Placebo in Healthy Male Subjects (Part 2).

Conditions
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Healthy Male Volunteers

Intervention / Treatment
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* Drug: BP1.5375 suspension
* Drug: Diphenhydramine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent prior to any study-mandated procedure. Healthy male subjects aged between 18 and 45 years (inclusive). Subjects with a body weight of at least 50 kg and a body mass index (BMI) between 18.0 and 28.0 kg/m2 (both inclusive). Healthy subjects, based on history, physical examination, complete laboratory evaluation, and 12-lead ECG. Normal arterial blood pressure (BP) and pulse rate or, if abnormal, considered not clinically significant by the investigator. Normal BP to be [100-140] mmHg systolic and [45-90] mmHg diastolic. Normal pulse rate to be [40-90] bpm after 5 minutes rest in lying position. Ability to communicate well with the investigator in the local language, and to understand and comply with the requirements of the study. Exclusion Criteria: Subject with a history of cardiovascular, pulmonary, gastro-intestinal, hepatic, renal, metabolic, haematological, neurological, psychiatric, systemic, or infectious disease, or any other condition which, in the opinion of the investigator, would jeopardize the safety of the subject, or impact the validity of the study results. Previous history of fainting, collapse, syncope, orthostatic hypotension, or vasovagal reactions. Haematology, clinical chemistry, and urinalysis results deviating from the normal range to a clinically relevant extent at screening. Clinically significant findings on physical examination at screening. 12-lead electrocardiogram (ECG) with clinically relevant abnormalities in supine position at screening. Positive results from urine drug screen at screening. Veins unsuitable for i.v. puncture on either arm (e.g., veins that are difficult to locate, access or puncture, or veins with a tendency for rupture during or after puncture). Treatment with any prescribed medications (including vaccines) or over-the-counter (OTC) medications (including herbal medicines such as St John's Wort) within 2 weeks prior to the (first) scheduled administration of study drug, except paracetamol (maximum 1 g/day). Treatment with another investigational drug within 3 months prior to screening or having participated in more than four investigational drug studies within 1 year prior to screening. History or clinical evidence of alcoholism or drug abuse within the 3-year period prior to screening. History or clinical evidence of any disease, and/or existence of any surgical or medical condition, which might interfere with the absorption, distribution, metabolism or excretion of the study drugs. Have undergone surgery or have donated an amount equal or more than 500 mL blood, or 300 mL of plasma, within 3 months prior to screening. Positive results from any of the hepatitis serology tests (HBsAg, anti-HCV), at screening. Positive results from the HIV 1 or/and 2 serology at screening. History of allergy to diphenhydramine or antihistaminic drugs. Smoking more than 5 cigarettes per day.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BP1.5375<br>Single oral administration ranging from 0.5 mg to 100 mg | Drug: BP1.5375 suspension<br>* single oral dose<br>Drug: Diphenhydramine<br>* single oral dose of Diphenhydramine 50mg<br>Drug: Placebo<br>* Single oral dose<br>|
| Active Comparator: Diphenhydramine<br>Single oral dose of diphenhydramine 50mg | Drug: BP1.5375 suspension<br>* single oral dose<br>Drug: Diphenhydramine<br>* single oral dose of Diphenhydramine 50mg<br>Drug: Placebo<br>* Single oral dose<br>|
| Placebo Comparator: Placebo<br>Single oral dose | Drug: BP1.5375 suspension<br>* single oral dose<br>Drug: Diphenhydramine<br>* single oral dose of Diphenhydramine 50mg<br>Drug: Placebo<br>* Single oral dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Single Ascending Dose - safety and tolerability (Part 1) | To determine the clinical and biological safety and tolerability of BP1.5375 after an oral increasing single dose administration BP1.5375. Physical examination : at screening and Follow-Up; a directed physical examination pre-dose and 24 hours post-dose, Vital signs : at screening, on day -2, on day 1 pre-dose then 0.5, 1, 1.5, 2, 3, 4, 8, 12 and 24 hours post dose and FU, Body temperature : at screening, on day -2, on day 1 pre-dose, then 24 hours post-dose and FU, Standard 12 lead ECG recording : at screening, on day -2, on day 1 pre-dose, then 0.5, 1, 2, 3, 4, 8, 12 and 24 hours post-dose and FU, Clinical laboratory tests: at screening, on day1 pre-dose, then 24 hours post-dose and FU, 48-hour 12 leads continuous ECG Holter recording from day -1 morning until dosing and from dosing until the morning of day 2. | Study period and follow up visit will be no more than 5 weeks | 
| Proof of Concept - effect on polysomnography (Part 2) | To determine whether an BP1.5375 single oral dose induced an effect on polysomnography in healthy male subjects compared to diphenhydramine 50 mg and matching placebo. Safety and tolerability : Monitoring for the occurrence of AEs, changes in physical examination, vital signs (body temperature, lying and standing blood pressure and heart rate), ECG, and clinical laboratory tests. Assessments will be performed at the following time points : Physical examination: at screening, on days 1 and FU, Vital signs: at screening, on days 1 and 2 and FU, Body temperature: at screening and FU, Standard 12 lead ECG recording : at screening, on days 1 and 2 morning and FU, Clinical laboratory tests : at screening, on days 1 and 2 and FU. | Study period and follow up visit will be no more than 9 weeks |