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

Ironwood Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Healthy Volunteers

Treatments: Drug: Microgestin®; Drug: Levothyroxine; Drug: IW-3718; Drug: Glyburide; Drug: Digoxin

Study type: Interventional

Funder types: Industry

Identifiers

NCT03856970

C3718-103

Details and patient eligibility

About

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.

Enrollment: 87 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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87 participants in 3 patient groups

Part 1: Healthy Volunteers

Experimental group

Description:

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).

Treatment:

Drug: IW-3718

Drug: Microgestin®

Part 2: Healthy Volunteers

Experimental group

Description:

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).

Treatment:

Drug: Levothyroxine

Drug: IW-3718

Part 3: Healthy Volunteers

Experimental group

Description:

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).

Treatment:

Drug: Glyburide

Drug: Digoxin

Drug: IW-3718