Study to Evaluate the Effect of IW-3718 on the Pharmacokinetics of Oral Contraceptive, Levothyroxine, Glyburide, and Digoxin in Healthy Adult Volunteers
Phase 1
Completed
- Conditions
- Healthy Volunteers
- Interventions
- Registration Number
- NCT03856970
- Lead Sponsor
- Ironwood Pharmaceuticals, Inc.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 87
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 1: Healthy Volunteers Microgestin® 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). Part 1: Healthy Volunteers IW-3718 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). Part 2: Healthy Volunteers Levothyroxine 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). Part 2: Healthy Volunteers IW-3718 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). Part 3: Healthy Volunteers IW-3718 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). Part 3: Healthy Volunteers Digoxin 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). Part 3: Healthy Volunteers Glyburide 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).
- Primary Outcome Measures
Name Time Method 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: 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 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
- Secondary Outcome Measures
Name Time Method 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
Trial Locations
- Locations (1)
PPD
🇺🇸Austin, Texas, United States