Study to Evaluate the Effect of IW-3718 on the Pharmacokinetics of Oral Contraceptive, Levothyroxine, Glyburide, and Digoxin in Healthy Adult Volunteers
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part 1: Healthy Volunteers 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®
30 μg/1500 μg tablets for oral administration
Other Names:
Drug: IW-3718
500-mg film-coated tablets for oral administration
|
| Experimental: Part 2: Healthy Volunteers 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
600 μg tablets for oral administration
Drug: IW-3718
500-mg film-coated tablets for oral administration
|
| Experimental: Part 3: Healthy Volunteers 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
5 mg tablets for oral administration
Drug: Digoxin
0.25 mg tablets for oral administration
Drug: IW-3718
500-mg film-coated tablets for oral administration
|
Outcome Measures
Primary Outcome Measures
- 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
- 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]
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | PPD | Austin | Texas | United States | 78744 |
Sponsors and Collaborators
- Ironwood Pharmaceuticals, Inc.
Investigators
- Study Director: Zurab Machaidze, MD, Ironwood Pharmaceuticals, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- C3718-103