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

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).

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

Study Overview

• Status: Terminated
• Conditions: Healthy Male Volunteers
• Intervention / Treatment: Drug: Placebo; Drug: BP1.5375 suspension; Drug: Diphenhydramine

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Leiden, Netherlands, 2333
    • Centre for Human Drug Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Bioprojet
• Investigators: Principal Investigator: van Gerven Joop, MD, Centre for Human Drug Research

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: October 11, 2013
• First Submitted That Met QC Criteria: October 17, 2013
• First Posted (Estimate): October 18, 2013

Study Record Updates

• Last Update Posted (Estimate): January 21, 2015
• Last Update Submitted That Met QC Criteria: January 20, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Antiemetics; Gastrointestinal Agents; Dermatologic Agents; Hypnotics and Sedatives; Anesthetics, Local; Anti-Allergic Agents; Sleep Aids, Pharmaceutical; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Antipruritics; Diphenhydramine; Promethazine
• Other Study ID Numbers: P12-03/BP1.5375; 2013-000697-30 (EudraCT Number)