A Trial of Intranasal Remimazolam Pharmacokinetics, Pharmacodynamics, Safety and Bioavailability

NCT03329014 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: CNS7056-019
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

A prospective dose escalation, nine period cross-over trial assessing the safety, pharmacokinetics, bioavailability and pharmacodynamics of escalating doses of Remimazolam when administered intranasally as powder and solution in healthy subjects and compared to an intravenous control

Conditions

Procedural Sedation

Outcome Measures

Primary Outcomes (1)

• Number of Participants with Treatment-related Adverse Events

  Adverse events assessment will include: change in clinical laboratory assessments from baseline, change in vital signs from baseline, change in 12-lead electrocardiograms from baseline, drop in oxygen saturation measured using continuous pulse oximetry, nasal effect using the Nasal Effect Questionnaire (NEQ) and nose and throat examination. Adverse events with a respiratory or cardiovascular focus and adverse events related to effects seen with medications known to be associated with abuse will be analysed separately. The intensity, causality, outcome, seriousness and expectedness of adverse events will be assessed

  Predose until 180 minutes postdose

Secondary Outcomes (12)

• Alertness/Drowsiness using a bipolar 100-point Visual Analogue Scale (VAS)

  Predose until 180 minutes postdose

• Agitation/Relaxation using a bipolar 100-point Visual Analogue Scale (VAS)

  Predose until 180 minutes postdose

• Any Drug Effects using a unipolar 100-point Visual Analogue Scale (VAS)

  Predose until 180 minutes postdose

• Memory/Amnestic Effects using the Paired Associates Learning (PALs) test

  Predose until 180 minutes postdose

• Reaction Time using the Reaction Time Test

  Predose until 180 minutes postdose

Study Arms (9)

Intravenous Remimazolam

EXPERIMENTAL

4 mg intravenous remimazolam as an intravenous control

Drug: Remimazolam

10 mg Powder Remimazolam

EXPERIMENTAL

Powder containing 10 mg remimazolam for intranasal administration

Drug: Remimazolam

10 mg Solution Remimazolam

EXPERIMENTAL

Solution containing 10 mg remimazolam for intranasal administration

Drug: Remimazolam

20 mg Powder Remimazolam

EXPERIMENTAL

Powder containing 20 mg remimazolam for intranasal administration

Drug: Remimazolam

20 mg solution Remimazolam

EXPERIMENTAL

Solution containing 20 mg remimazolam for intranasal administration

Drug: Remimazolam

40 mg Powder Remimazolam

EXPERIMENTAL

Powder containing 40 mg remimazolam for intranasal administration

Drug: Remimazolam

40 mg Solution Remimazolam

EXPERIMENTAL

Solution containing 40 mg remimazolam for intranasal administration

Drug: Remimazolam

Placebo Powder

PLACEBO COMPARATOR

Powder containing 20 mg placebo for intranasal administration

Drug: Placebo

Placebo solution

PLACEBO COMPARATOR

Solution containing 20 mg placebo for intranasal administration

Drug: Placebo

Interventions

Remimazolam DRUG

For induction and maintenance of sedation

Also known as: CNS7056

10 mg Powder Remimazolam; 10 mg Solution Remimazolam; 20 mg Powder Remimazolam; 20 mg solution Remimazolam; 40 mg Powder Remimazolam; 40 mg Solution Remimazolam; Intravenous Remimazolam

Placebo DRUG

Control arm

Placebo Powder; Placebo solution

Eligibility Criteria

• Age: 18 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 to comply with the study restrictions.
• Able to speak, read and understand English sufficiently to allow completion of all study assessments.
• Gender: males
• Age: 18 45 years, inclusive, at screening
• Weight: 50 to 120 kg, inclusive, at screening
• Body mass index: 19.0 to 33.0 kg/m2, inclusive, at screening
• Healthy status, defined by the absence of evidence of any clinically significant, active or chronic diseases, in the opinion of the Investigator, following a detailed medical and surgical history, a complete physical examination, and evaluation of vital signs, 12 lead ECG, hematology, blood chemistry, serology, and urinalysis.
• Previous experience with intranasal drug application (within the last year)
• Ability and willingness to abstain from alcohol, caffeine, and xanthine containing beverages or food (e.g., coffee, tea, cola, chocolate, energy drinks) from 24 hours (1 day) prior to admission to the clinical facility on Day 0 until study 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.

You may not qualify if:

• Use of any intranasally applied medication within two weeks from randomization.
• History of alcohol abuse or drug addiction (except nicotine), 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).
• Abnormal 12 lead ECG at screening, including:
• QTcF ≥ 450 ms
• QRS ≥ 110 ms
• PR ≥ 220 ms
• Second or third degree AV block
• Use of any investigational drug or device within 30 days of the first dose of study medication.
• History of relevant food allergies.
• Any disease which, in the opinion of the Investigator, poses 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 are contraindicated.
• Strenuous activity, sunbathing, and contact sports within 48 hours (2 days) prior to (first) admission to the clinical facility and for the duration of the study.
• 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 has elapsed since intake of study drug in the current study.
• 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 \[including ecstasy\], barbiturates, benzodiazepines, tricyclic antidepressants and alcohol) at screening and at admission to the clinical research center; subjects positive for cannabinoids will be allowed only at the discretion of the Investigator.

Sponsors & Collaborators

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

Study Sites (1)

PRA Health Sciences

Salt Lake City, Utah, 84106, United States

Location

MeSH Terms

Interventions

remimazolam

Study Officials

• Shawn Searly, M.D

  PRA Health Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 2, 2017
• First Posted: November 1, 2017
• Study Start: May 15, 2017
• Primary Completion: June 9, 2017
• Study Completion: June 14, 2017
• Last Updated: April 4, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)