Clinical trial NCT03856970: Study to Evaluate the Effect of IW-3718 on the Pharmacokinetics of Oral Contraceptive, Levothyroxine, Glyburide, and Digoxin in Healthy Adult Volunteers
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Ironwood Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2019-02-27
Enrollment: 87
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: PK of EE and NET: Area Under the Plasma Concentration Versus Time Curve (AUC) From Time 0 to the Last Quantifiable Concentration (AUC0-t)
timeFrame: Treatment Period 1 (Days 1-6) and Treatment Period 2 (Days 14-19): predose, up to 120 hours postdose
measure: PK of EE and NET: AUC From Time 0 Extrapolated to Infinity (AUC0-inf)
timeFrame: Treatment Period 1 (Days 1-6) and Treatment Period 2 (Days 14-19): predose, up to 120 hours postdose
measure: PK of EE and NET: Maximum Observed Plasma Concentration (Cmax)
timeFrame: Treatment Period 1 (Days 1-6) and Treatment Period 2 (Days 14-19): predose, up to 120 hours postdose
measure: PK of EE and NET: Time to Maximum Observed Plasma Concentration (Tmax)
timeFrame: Treatment Period 1 (Days 1-6) and Treatment Period 2 (Days 14-19): predose, up to 120 hours postdose
measure: PK of EE and NET: Terminal Phase Half-Life (t1/2)
timeFrame: Treatment Period 1 (Days 1-6) and Treatment Period 2 (Days 14-19): predose, up to 120 hours postdose
measure: PK of Levothyroxine: AUC0-t
timeFrame: Treatment Period 1 (Days 1-3) and Treatment Period 2 (Days 39-41): predose, up to 48 hours postdose
measure: PK of Levothyroxine: AUC0-inf
timeFrame: Treatment Period 1 (Days 1-3) and Treatment Period 2 (Days 39-41): predose, up to 48 hours postdose
measure: PK of Levothyroxine: Cmax
timeFrame: Treatment Period 1 (Days 1-3) and Treatment Period 2 (Days 39-41): predose, up to 48 hours postdose
measure: PK of Levothyroxine: Tmax
timeFrame: Treatment Period 1 (Days 1-3) and Treatment Period 2 (Days 39-41): predose, up to 48 hours postdose
measure: PK of Levothyroxine: t1/2
timeFrame: Treatment Period 1 (Days 1-3) and Treatment Period 2 (Days 39-41): predose, up to 48 hours postdose
measure: PK of Glyburide: AUC0-t
timeFrame: Treatment Period 1 (Days 1-4) and Treatment Period 2 (Days 11-14): predose, up to 72 hours postdose
measure: PK of Glyburide: AUC0-inf
timeFrame: Treatment Period 1 (Days 1-4) and Treatment Period 2 (Days 11-14): predose, up to 72 hours postdose
measure: PK of Glyburide: Cmax
timeFrame: Treatment Period 1 (Days 1-4) and Treatment Period 2 (Days 11-14): predose, up to 72 hours postdose
measure: PK of Glyburide: Tmax
timeFrame: Treatment Period 1 (Days 1-4) and Treatment Period 2 (Days 11-14): predose, up to 72 hours postdose
measure: PK of Glyburide: t1/2
timeFrame: Treatment Period 1 (Days 1-4) and Treatment Period 2 (Days 11-14): predose, up to 72 hours postdose
measure: PK of Digoxin: AUC0-t
timeFrame: Treatment Period 1 (Days 23-30) and Treatment Period 2 (Days 35-42): predose, up to 168 hours postdose
measure: PK of Digoxin: AUC0-inf
timeFrame: Treatment Period 1 (Days 23-30) and Treatment Period 2 (Days 35-42): predose, up to 168 hours postdose
measure: PK of Digoxin: Cmax
timeFrame: Treatment Period 1 (Days 23-30) and Treatment Period 2 (Days 35-42): predose, up to 168 hours postdose
measure: PK of Digoxin: Tmax
timeFrame: Treatment Period 1 (Days 23-30) and Treatment Period 2 (Days 35-42): predose, up to 168 hours postdose
measure: PK of Digoxin: t1/2
timeFrame: Treatment Period 1 (Days 23-30) and Treatment Period 2 (Days 35-42): predose, up to 168 hours postdose
Secondary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations due to TEAEs
timeFrame: Part 1: up to Day 27 (±1 day); Part 2: up to Day 49 (±1 day); Part 3: Day 50 (±1 day)
measure: Number of Participants With ≥1 Clinically Significant Changes in Clinical Laboratory Test Results
timeFrame: Part 1: up to Day 19; Part 2: up to Day 41; Part 3: up to Day 42
measure: Number of Participants With ≥1 Clinically Significant Changes in Vital Sign Measurements
timeFrame: Part 1: up to Day 19; Part 2: up to Day 41; Part 3: up to Day 42
measure: Number of Participants With ≥1 Clinically Significant Changes in 12-lead Electrocardiogram (ECG) Results
timeFrame: Part 1: up to Day 19; Part 2: up to Day 41; Part 3: up to Day 42
measure: Number of Participants With ≥1 Clinically Significant Changes in Physical Examination Findings
timeFrame: Part 1: up to Day 19; Part 2: up to Day 41; Part 3: up to Day 42
Other outcomes:
Locations:
city: Austin
country: United States
facility: PPD
state: Texas
Study officials:
affiliation: Ironwood Pharmaceuticals, Inc.
name: Zurab Machaidze, MD
role: STUDY_DIRECTOR
References: