A Trial to Evaluate the Effect of Itraconazole (ITZ), a CYP3A4 Inhibitor, on the Pharmacokinetics of the Soluble Guanylate Cyclase Stimulator, Olinciguat (IW-1701), in Healthy Volunteers

An Open-label, 2-Period, Fixed-sequence, Phase 1 Study in Healthy Volunteers to Evaluate the Effect of Itraconazole, a Potent CYP3A Inhibitor, on the Pharmacokinetics of Olinciguat (IW-1701)

To evaluate the effect of itraconazole (a potent cytochrome P450 isoenzyme [CYP]3A inhibitor) on the pharmacokinetics (PK) of olinciguat

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Itraconazole; Drug: Olinciguat

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78744
      • PPD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject is an ambulatory adult and between 18 and 55 years old (inclusive) at the screening visit
• Subject is in good health and has no clinically significant findings on physical examination
• Body mass index is > 18 and < 30 kg/m2 at the screening visit
• Women of reproductive potential must have a negative pregnancy test at screening at at the time of check-in and must agree to use protocol-specified contraception throughout the duration of the study and until 90 days after receiving the final study drug dose
• Men must agree to use protocol-specified contraception and also to not donate sperm throughout the study and until 90 days after receiving the final study drug dose
• Other inclusion criteria per protocol

Exclusion Criteria:

• Any active or unstable clinically significant medical condition
• Use of any prescribed or non-prescribed medication (except for hormonal birth control)
• Other exclusion criteria per protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Healthy Volunteers; Period 1: Single dose of olinciguat. Period 2: ITZ is dosed once daily (QD) for 10 days; a single dose of olinciguat is administered 1 hour after the fourth ITZ QD dose.	Drug: Itraconazole; Oral Capsule; Drug: Olinciguat; Oral Tablet; Other Names: IW-1701

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum Observed Plasma Concentration (Cmax) of olinciguat	Predose and up to 8 days post first olinciguat dose
Area under the plasma concentration time curve from time zero (predose) extrapolated to infinity (AUCinf)	Predose and up to 8 days post first olinciguat dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of subjects with ≥1 treatment-emergent adverse event (TEAE) in Period 1 vs Period 2	51 days post first olinciguat dose
Cmax of Itraconazole	First Itraconazole dose up to day 8 of Period 2 (Period 2 duration can be up to 13 days)
Area under the concentration-time curve during a dosing interval (AUCtau) for itraconazole and hydroxy-itraconazole	Period 2 (Period 2 duration can be up to 13 days) predose and up to 24 hour after 2nd olinciguat dose
Cmax of hydroxy-Itraconazole	First Itraconazole dose up to day 8 of Period 2 (Period 2 duration can be up to 13 days)

Collaborators and Investigators

• Sponsor: Cyclerion Therapeutics
• Investigators: Study Director: Bina Tejura, MD, Cyclerion Therapeutics

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 3, 2019
• Primary Completion (ACTUAL): June 23, 2019
• Study Completion (ACTUAL): July 3, 2019

Study Registration Dates

• First Submitted: March 25, 2019
• First Submitted That Met QC Criteria: March 26, 2019
• First Posted (ACTUAL): March 27, 2019

Study Record Updates

• Last Update Posted (ACTUAL): July 15, 2019
• Last Update Submitted That Met QC Criteria: July 11, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Itraconazole
• Other Study ID Numbers: OLI-105

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