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

Ironwood Pharmaceuticals, Inc.87 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Healthy Volunteers

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 50 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

PK of EE and NET: Area Under the Plasma Concentration Versus Time Curve (AUC) From Time 0 to the Last Quantifiable Concentration (AUC0-t)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: Treatment Period 1 (Days 1-6) and Treatment Period 2 (Days 14-19): predose, up to 120 hours postdose

PK of Levothyroxine: AUC0-t

Time frame: Treatment Period 1 (Days 1-3) and Treatment Period 2 (Days 39-41): predose, up to 48 hours postdose

PK of Levothyroxine: AUC0-inf

Time frame: Treatment Period 1 (Days 1-3) and Treatment Period 2 (Days 39-41): predose, up to 48 hours postdose

PK of Levothyroxine: Cmax

Time frame: Treatment Period 1 (Days 1-3) and Treatment Period 2 (Days 39-41): predose, up to 48 hours postdose

PK of Levothyroxine: Tmax

Time frame: Treatment Period 1 (Days 1-3) and Treatment Period 2 (Days 39-41): predose, up to 48 hours postdose

PK of Levothyroxine: t1/2

Time frame: Treatment Period 1 (Days 1-3) and Treatment Period 2 (Days 39-41): predose, up to 48 hours postdose

PK of Glyburide: AUC0-t

Time frame: Treatment Period 1 (Days 1-4) and Treatment Period 2 (Days 11-14): predose, up to 72 hours postdose

PK of Glyburide: AUC0-inf

Time frame: Treatment Period 1 (Days 1-4) and Treatment Period 2 (Days 11-14): predose, up to 72 hours postdose

PK of Glyburide: Cmax

Time frame: Treatment Period 1 (Days 1-4) and Treatment Period 2 (Days 11-14): predose, up to 72 hours postdose

PK of Glyburide: Tmax

Time frame: Treatment Period 1 (Days 1-4) and Treatment Period 2 (Days 11-14): predose, up to 72 hours postdose

PK of Glyburide: t1/2

Time frame: Treatment Period 1 (Days 1-4) and Treatment Period 2 (Days 11-14): predose, up to 72 hours postdose

PK of Digoxin: AUC0-t