Study to Evaluate the Effect of IW-3718 on the Pharmacokinetics of Oral Contraceptive, Levothyroxine, Glyburide, and Digoxin in Healthy Adult Volunteers

Study Overview
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Brief Summary
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The primary objectives of this study are the following: To evaluate the pharmacokinetics (PK) of a monophasic oral contraceptive's active components, ethinyl estradiol (EE) and norethindrone acetate (NET), following a single oral dose alone and in combination with IW-3718 in healthy adult female participants. To evaluate the PK of levothyroxine following a single oral dose alone and in combination with IW-3718 in healthy adult participants. To evaluate the PK of glyburide following a single oral dose alone and in combination with IW-3718 in healthy adult participants. To evaluate the PK of digoxin following a single oral dose alone and in combination with IW-3718 in healthy adult participants.

Official Title
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A Phase 1, Open-Label, Parallel, Sequential, Multi-part Study to Evaluate the Effect of IW-3718 on the Pharmacokinetics of an Oral Contraceptive, Levothyroxine, Glyburide, and Digoxin in Healthy Adult Volunteers

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Microgestin®
* Drug: Levothyroxine
* Drug: Glyburide
* Drug: Digoxin
* Drug: IW-3718


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is healthy, ambulatory, and 18-50 years of age (inclusive) at screening visit. Weighs at least 50 kg and has a body mass index within 18-35 kg/m2 at the screening visit. Is not pregnant or breastfeeding at the time of the screening visit and has negative serum pregnancy tests at the screening visit and check-in. Other inclusion criteria per protocol. Exclusion Criteria: Has used any prescription drugs, herbal supplements, over-the-counter medication, or dietary supplements (vitamins included) within 4 weeks prior to dosing. If needed, (ie, incidental and limited need), acetaminophen is acceptable. Has consumed grapefruit or grapefruit juice within 4 weeks prior to dosing or plans to consume grapefruit or grapefruit juice before 7 days following the last dose. Has a significant illness that has not resolved within 2 weeks prior to dosing. Has a history of immunodeficiency diseases, including a positive human immunodeficiency virus test result. Has a positive hepatitis B surface antigen or hepatitis C antibody test result. Is a smoker or has used nicotine or nicotine-containing products (eg, snuff, nicotine patch, nicotine chewing gum, mock cigarettes, or inhalers) within 6 months before the first dose of study drug. Other exclusion criteria per protocol.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: Healthy Volunteers<br>Microgestin® (EE 30 μg and NET 1500 μg) single dose (Day 1). After a 10-14 day washout, Microgestin® single dose (Day 14) PLUS IW-3718 1500 mg twice daily (Days 13 to 19). | Drug: Microgestin®<br>* 30 μg/1500 μg tablets for oral administration<br>* Other names: ethinyl estradiol 30 μg and norethindrone 1500 μg;Drug: IW-3718<br>* 500-mg film-coated tablets for oral administration<br>|
| Experimental: Part 2: Healthy Volunteers<br>Levothyroxine 600 μg single dose (Day 1). After a 35-39 day washout, levothyroxine 600 μg single dose (Day 39) PLUS IW-3718 1500 mg twice daily (Days 38 to 41). | Drug: Levothyroxine<br>* 600 μg tablets for oral administration<br>Drug: IW-3718<br>* 500-mg film-coated tablets for oral administration<br>|
| Experimental: Part 3: Healthy Volunteers<br>Phase 1: Glyburide 5 mg single dose (Day 1). After a 7-10 day washout, glyburide 5 mg single dose (Day 11) PLUS IW-3718 1500 mg twice daily (ie, Days 10 to 14). Phase 2: Digoxin 0.25 mg single dose (Day 23). After a 10-14 day washout, digoxin 0.25 mg mg single dose (Day 35) PLUS IW-3718 1500 mg twice daily (Days 34 to 42). | Drug: Glyburide<br>* 5 mg tablets for oral administration<br>Drug: Digoxin<br>* 0.25 mg tablets for oral administration<br>Drug: IW-3718<br>* 500-mg film-coated tablets for oral administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK of EE and NET: Area Under the Plasma Concentration Versus Time Curve (AUC) From Time 0 to the Last Quantifiable Concentration (AUC0-t) |  | Treatment Period 1 (Days 1-6) and Treatment Period 2 (Days 14-19): predose, up to 120 hours postdose | 
| PK of EE and NET: AUC From Time 0 Extrapolated to Infinity (AUC0-inf) |  | Treatment Period 1 (Days 1-6) and Treatment Period 2 (Days 14-19): predose, up to 120 hours postdose | 
| PK of EE and NET: Maximum Observed Plasma Concentration (Cmax) |  | Treatment Period 1 (Days 1-6) and Treatment Period 2 (Days 14-19): predose, up to 120 hours postdose | 
| PK of EE and NET: Time to Maximum Observed Plasma Concentration (Tmax) |  | Treatment Period 1 (Days 1-6) and Treatment Period 2 (Days 14-19): predose, up to 120 hours postdose | 
| PK of EE and NET: Terminal Phase Half-Life (t1/2) |  | Treatment Period 1 (Days 1-6) and Treatment Period 2 (Days 14-19): predose, up to 120 hours postdose | 
| PK of Levothyroxine: AUC0-t |  | Treatment Period 1 (Days 1-3) and Treatment Period 2 (Days 39-41): predose, up to 48 hours postdose | 
| PK of Levothyroxine: AUC0-inf |  | Treatment Period 1 (Days 1-3) and Treatment Period 2 (Days 39-41): predose, up to 48 hours postdose | 
| PK of Levothyroxine: Cmax |  | Treatment Period 1 (Days 1-3) and Treatment Period 2 (Days 39-41): predose, up to 48 hours postdose | 
| PK of Levothyroxine: Tmax |  | Treatment Period 1 (Days 1-3) and Treatment Period 2 (Days 39-41): predose, up to 48 hours postdose | 
| PK of Levothyroxine: t1/2 |  | Treatment Period 1 (Days 1-3) and Treatment Period 2 (Days 39-41): predose, up to 48 hours postdose | 
| PK of Glyburide: AUC0-t |  | Treatment Period 1 (Days 1-4) and Treatment Period 2 (Days 11-14): predose, up to 72 hours postdose | 
| PK of Glyburide: AUC0-inf |  | Treatment Period 1 (Days 1-4) and Treatment Period 2 (Days 11-14): predose, up to 72 hours postdose | 
| PK of Glyburide: Cmax |  | Treatment Period 1 (Days 1-4) and Treatment Period 2 (Days 11-14): predose, up to 72 hours postdose | 
| PK of Glyburide: Tmax |  | Treatment Period 1 (Days 1-4) and Treatment Period 2 (Days 11-14): predose, up to 72 hours postdose | 
| PK of Glyburide: t1/2 |  | Treatment Period 1 (Days 1-4) and Treatment Period 2 (Days 11-14): predose, up to 72 hours postdose | 
| PK of Digoxin: AUC0-t |  | Treatment Period 1 (Days 23-30) and Treatment Period 2 (Days 35-42): predose, up to 168 hours postdose | 
| PK of Digoxin: AUC0-inf |  | Treatment Period 1 (Days 23-30) and Treatment Period 2 (Days 35-42): predose, up to 168 hours postdose | 
| PK of Digoxin: Cmax |  | Treatment Period 1 (Days 23-30) and Treatment Period 2 (Days 35-42): predose, up to 168 hours postdose | 
| PK of Digoxin: Tmax |  | Treatment Period 1 (Days 23-30) and Treatment Period 2 (Days 35-42): predose, up to 168 hours postdose | 
| PK of Digoxin: t1/2 |  | Treatment Period 1 (Days 23-30) and Treatment Period 2 (Days 35-42): predose, up to 168 hours postdose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations due to TEAEs |  | Part 1: up to Day 27 (±1 day); Part 2: up to Day 49 (±1 day); Part 3: Day 50 (±1 day) | 
| Number of Participants With ≥1 Clinically Significant Changes in Clinical Laboratory Test Results |  | Part 1: up to Day 19; Part 2: up to Day 41; Part 3: up to Day 42 | 
| Number of Participants With ≥1 Clinically Significant Changes in Vital Sign Measurements |  | Part 1: up to Day 19; Part 2: up to Day 41; Part 3: up to Day 42 | 
| Number of Participants With ≥1 Clinically Significant Changes in 12-lead Electrocardiogram (ECG) Results |  | Part 1: up to Day 19; Part 2: up to Day 41; Part 3: up to Day 42 | 
| Number of Participants With ≥1 Clinically Significant Changes in Physical Examination Findings |  | Part 1: up to Day 19; Part 2: up to Day 41; Part 3: up to Day 42 |