Oral Remimazolam With and Without Alcohol in Healthy Female Subjects

NCT04113343 | Completed Phase 1 FDA Drug

• 1 other identifier: CNS7056-020
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

A Phase 1 Study to Determine the Single-dose Pharmacodynamics, Pharmacokinetics, and Safety and Tolerability of Remimazolam Following Oral Administration With and Without Alcohol in Healthy Female Subjects

Conditions

Safety Issues

Keywords

remimazolam

Outcome Measures

Primary Outcomes (10)

• Paired Associates Learning (PAL) Test

  PAL Test was conducted using the software CANTAB (Cambridge Cognition)

  Predose to 4 hours postdose

• Modified Observer Assessment of Alertness/Sedation (MOAA/S)

  The MOAA/S scale is a validated, 6-point rating scale that involves an observer rating subjects' responsiveness to stimuli of increasing intensity (5 = alert, 0 = sedated).

  Predose to 4 hours postdose

• Alertness/Drowsiness Visual Analog Scale (VAS)

  The Alertness/Drowsiness VAS was administered as a 100-point bipolar scale, with 50 being the neutral point, as follows:0: Very drowsy, 50: Neither drowsy nor alert, 100: Very alert

  Predose to 4 hours postdose

• Reaction Time Test (RTI)

  RTI was conducted using the software CANTAB (Cambridge Cognition).

  Predose to 4 hours postdose

• Maximum observed plasma concentration (Cmax)

  Predose to 8 hours postdose

• Time to Maximum observed plasma concentration (Tmax)

  Predose to 8 hours postdose

• Area under the plasma concentration-time curve (AUC) from zero to the last measurable concentration

  Predose to 8 hours postdose

• Terminal elimination half-life (T1/2)

  Predose to 8 hours postdose

• Apparent oral clearance (CL/F)

  Predose to 8 hours postdose

• Apparent volume of distribution at terminal Phase (Vz/F)

  Predose to 8 hours postdose

Study Arms (5)

Treatment A: remimazolam

ACTIVE COMPARATOR

Oral administration of 360 mg remimazolam

Drug: Remimazolam

Treatment B: remimazolam + 5% v/v alcohol

EXPERIMENTAL

Oral administration of 360 mg remimazolam and 5% v/v alcohol

Drug: Remimazolam; Other: Alcohol

Treatment C: remimazolam + 15% v/v alcohol

EXPERIMENTAL

Oral administration of 360 mg remimazolam + 15% v/v alcohol

Drug: Remimazolam; Other: Alcohol

Treatment D: remimazolam + 40% v/v alcohol

EXPERIMENTAL

Oral administration of 360 mg remimazolam + 40% v/v alcohol

Drug: Remimazolam; Other: Alcohol

Treatment E: placebo + 40% v/v alcohol

PLACEBO COMPARATOR

Oral administration of Placebo + 40% v/v alcohol

Other: Alcohol

Interventions

Remimazolam DRUG

Remimazolam via oral administration

Also known as: CNS7056

Treatment A: remimazolam; Treatment B: remimazolam + 5% v/v alcohol; Treatment C: remimazolam + 15% v/v alcohol; Treatment D: remimazolam + 40% v/v alcohol

Alcohol OTHER

Alcohol

Treatment B: remimazolam + 5% v/v alcohol; Treatment C: remimazolam + 15% v/v alcohol; Treatment D: remimazolam + 40% v/v alcohol; Treatment E: placebo + 40% v/v alcohol

Eligibility Criteria

• Age: 21 Years - 45 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Willing to participate in the trial, give written informed consent prior to the initiation of any protocol-specific procedures, and comply with the trial restrictions.
• Able to speak, read, and understand English sufficiently to allow completion of all Trial assessments.
• Gender : female
• Age : 21 to 45 years, inclusive
• Weight : ≥ 50 kg
• Body mass index (BMI) : 18.0 to 33.0 kg/m2, inclusive
• Healthy status, defined by the absence of evidence of any clinically significant, in the opinion of the Investigator, active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead electrocardiograms (ECG), hematology, blood chemistry, serology, and urinalysis.
• Current alcohol user classified as a moderate drinker, defined as drinking \> 2 drinks/week and ≤ 14 drinks/week (1 drink equals approximately 12 oz/350 mL of beer, 5 oz/150 mL of wine, or 1.5 oz/45 mL of spirits).6
• Ability and willingness to abstain from alcohol, caffeine, and xanthine-containing beverages or food (eg, coffee, tea, cola, chocolate, energy drinks) from 48 hours (2 days) prior to admission to the clinical facility on Day -1 until trial discharge.
• All values for hematology and for clinical chemistry tests of blood and urine within the normal range or showing no clinically relevant deviations, as judged by the Investigator.
• A negative pregnancy test at Screening and Day -1.
• Females of childbearing potential must have agreed to use 2 forms of contraception, one of which must have been a barrier method, during the trial and for 90 days after the last drug administration. Acceptable barrier forms of contraception were condom and diaphragm. Acceptable nonbarrier forms of contraception for this trial were oral contraceptives, injectable hormone contraceptives, implantable birth control, intrauterine devices, and/or spermicide. Injectable hormonal contraception was allowable as a nonbarrier method.
• Females who were not of childbearing potential, including postmenopausal females (defined as 12 months with no menses prior to Screening and a serum follicle-stimulating hormone \[FSH\] \> 40 IU/L at Screening) or females who were surgically sterilized.

You may not qualify if:

• Females who were pregnant or lactating.
• Known intolerance towards alcohol (symptoms could include nausea, flushed face, vomiting, or hypotension upon drinking) or known alcohol dehydrogenase deficiency.
• of Asian descent (one or both parents) due to potential for genetic polymorphism related to aldehyde dehydrogenase deficiency.
• History of alcohol abuse or drug addiction (except nicotine or caffeine), as defined by the Diagnostic and Statistical Manual of Mental Disorders, fifth edition, text Revision (DSM-V-TR), or any self-reported dependence or "addiction" within the subject's lifetime (except nicotine or caffeine).
• History of relevant food allergies.
• Use of any investigational drug or device within 30 days of the first dose of Trial medication.
• Any disease which, in the opinion of the Investigator, posed an unacceptable risk to the subjects.
• Known allergy, hypersensitivity, or prior intolerance to benzodiazepine derivatives or flumazenil, or a medical condition such that these agents were contraindicated.
• Use of tobacco products within 60 days prior to the first drug administration.
• Routine or chronic use of more than 3 grams of acetaminophen daily.
• History of donation or loss of more than 450 mL of blood or blood products within 60 days prior to dosing in the clinical research center or planned donation before 30 days had elapsed since intake of trial drug in the current trial.
• Positive screening test for hepatitis B surface antigen (HBsAg), anti-hepatitis C Virus (HCV) antibodies, or anti-human immunodeficiency virus (HIV) 1 and 2 antibodies.
• Positive drug and alcohol screen (opiates, methadone, cocaine, amphetamines \[including ecstasy\], cannabinoids, barbiturates, benzodiazepines, tricyclic antidepressants, and alcohol) at Screening and admission to the clinical research center.
• Average intake of \> 14 drinks of alcohol per week (1 drink equals approximately 12 oz/350 mL of beer, 5 oz/150 mL of wine, or 1.5 oz/45 mL of spirits).
• Required concomitant treatment with any prescription or non-prescription medications (with the exception of hormonal contraceptives, hormone replacement, and acetaminophen) or natural health products (herbal remedies), or respiratory depressants, or could not safely discontinue these medications at least 7 days prior to receiving trial drug.

Sponsors & Collaborators

• Paion UK Ltd.: lead
• PRA Health Sciences: collaborator

Study Sites (1)

PRA Health Sciences (PRA) - Early Development Services

Salt Lake City, Utah, 84106, United States

Location

Related Publications (1)

• Pesic M, Stohr T, Ossig J, Borkett K, Donsbach M, Dao VA, Webster L, Schippers F. Remimazolam Has Low Oral Bioavailability and No Potential for Misuse in Drug-Facilitated Sexual Assaults, with or Without Alcohol: Results from Two Randomised Clinical Trials. Drugs R D. 2020 Sep;20(3):267-277. doi: 10.1007/s40268-020-00317-0.

  PMID: 32757149 DERIVED

MeSH Terms

Interventions

remimazolam; Ethanol

Intervention Hierarchy (Ancestors)

Alcohols; Organic Chemicals

Study Officials

• Ahad Sabet, MD

  PRA Health Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2019
• First Posted: October 2, 2019
• Study Start: May 30, 2017
• Primary Completion: August 9, 2017
• Study Completion: August 9, 2017
• Last Updated: October 2, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)