Pharmacokinetic Interaction Between Midazolam and ID-082 in Healthy Subjects

A Single-center, Open-label Study to Investigate the Effect of a Single Oral Dose and Repeated Oral Doses of ID-082 on the Pharmacokinetics of Midazolam and Its Metabolite 1-hydroxymidazolam in Healthy Male Subjects.

A clinical study in healthy male subjects to investigate whether the administration of ID-082 can affect the fate in the body (amount and time of presence in the blood) of midazolam.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Midazolam; Drug: ID-082

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Mid Galmorgan
    • Merthyr Tydfil, Mid Galmorgan, United Kingdom, CF48 4DR
      • Simbec Research Limited

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 in the local language prior to any study-mandated procedure;
• Healthy male subjects aged 18 to 45 years (inclusive) at screening;
• Male subject with a female partner of childbearing potential or a pregnant partner must agree to use a condom from screening, during the study, and for at least 3 months after last study treatment intake;
• Body mass index of 18.0 to 30.0 kg/m2 (inclusive) at screening;
• Healthy on the basis of physical examination, cardiovascular assessments and laboratory tests.

Exclusion Criteria:

• Contraindication or known hypersensitivity to ID-082, midazolam or drugs of the same classes, or any of their excipients;
• Modified Swiss Narcolepsy Scale total score < 0 at Screening or history of narcolepsy or cataplexy;
• 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 treatment;
• Known hypersensitivity or allergy to natural rubber latex;
• Known hereditary problems of fructose intolerance, glucose-galactose malabsorption, or sucrose-isomaltase insufficiency;
• Previous history of fainting, collapse, syncope, orthostatic hypotension, or vasovagal reactions;
• Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Midazolam & ID-082; Single oral administration of 2 mg midazolam on Day 1, Day 2, and Day 11. Administration of ID-082 from Day 2 through Day 11.	Drug: Midazolam; Single oral administration of 2 mg midazolam under fasted conditions/outside of meal times; Drug: ID-082; Administration of ID-082 under fasted conditions/outside of meal times

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax of midazolam	Maximum plasma concentration	From baseline to EOS (i.e. for up to 16 days)
AUC0-24 of midazolam	Area under the plasma concentration-time curvefrom time zero to 24 h	From baseline to EOS (i.e. for up to 16 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax of 1-hydroxymidazolam	Maximum plasma concentration	From baseline to EOS (i.e. for up to 16 days)
AUC0-inf of midazolam and 1-hydroxymidazolam and AUC0-24 of 1-hydroxymidazolam	Area under the plasma concentration-time curve from zero to infinity	From baseline to EOS (i.e. for up to 16 days)
tmax of midazolam and 1-hydroxymidazolam	Time to reach maximum plasma concentration	From baseline to EOS (i.e. for up to 16 days)
t½ of midazolam and 1-hydroxymidazolam	Terminal elimination half-life	From baseline to EOS (i.e. for up to 16 days)
Total body apparent plasma clearance (CL/F) of midazolam		From baseline to EOS (i.e. for up to 16 days)
Metabolic ratio (MR) of the AUC0-24 of 1-hydroxymidazolam to the AUC0-24 of midazolam		From baseline to EOS (i.e. for up to 16 days)

Collaborators and Investigators

• Sponsor: Idorsia Pharmaceuticals Ltd.
• Investigators: Study Director: Fabienne Le Gac, Idorsia Pharmaceuticals Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): November 27, 2017
• Primary Completion (Actual): December 19, 2017
• Study Completion (Actual): December 19, 2017

Study Registration Dates

• First Submitted: November 21, 2017
• First Submitted That Met QC Criteria: November 30, 2017
• First Posted (Actual): December 6, 2017

Study Record Updates

• Last Update Posted (Actual): June 27, 2018
• Last Update Submitted That Met QC Criteria: June 26, 2018
• Last Verified: June 1, 2018

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; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Midazolam
• Other Study ID Numbers: ID-082-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No