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

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

Official Title
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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)

Conditions
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Healthy

Intervention / Treatment
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* Drug: Olinciguat
* Drug: Itraconazole


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Healthy Volunteers<br>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: Olinciguat<br>* Oral Tablet<br>* Other names: IW-1701;Drug: Itraconazole<br>* Oral Capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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) |