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

Healthy Volunteers Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03856970
• Other study ID #: C3718-103
• Status: Completed
• Phase: Phase 1
• Start date: March 11, 2019
• Est. completion date: July 3, 2019

Study information

• Verified date: July 2019
• Source: Ironwood Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 87
• Est. completion date: July 3, 2019
• Est. primary completion date: June 25, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• Microgestin®
30 µg/1500 µg tablets for oral administration
• Levothyroxine
600 µg tablets for oral administration
• Glyburide
5 mg tablets for oral administration
• Digoxin
0.25 mg tablets for oral administration
• IW-3718
500-mg film-coated tablets for oral administration

Locations

Country	Name	City	State
United States	PPD	Austin	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Ironwood Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	PK of Levothyroxine: AUC0-t		Treatment Period 1 (Days 1-3) and Treatment Period 2 (Days 39-41): predose, up to 48 hours postdose
Primary	PK of Levothyroxine: AUC0-inf		Treatment Period 1 (Days 1-3) and Treatment Period 2 (Days 39-41): predose, up to 48 hours postdose
Primary	PK of Levothyroxine: Cmax		Treatment Period 1 (Days 1-3) and Treatment Period 2 (Days 39-41): predose, up to 48 hours postdose
Primary	PK of Levothyroxine: Tmax		Treatment Period 1 (Days 1-3) and Treatment Period 2 (Days 39-41): predose, up to 48 hours postdose
Primary	PK of Levothyroxine: t1/2		Treatment Period 1 (Days 1-3) and Treatment Period 2 (Days 39-41): predose, up to 48 hours postdose
Primary	PK of Glyburide: AUC0-t		Treatment Period 1 (Days 1-4) and Treatment Period 2 (Days 11-14): predose, up to 72 hours postdose
Primary	PK of Glyburide: AUC0-inf		Treatment Period 1 (Days 1-4) and Treatment Period 2 (Days 11-14): predose, up to 72 hours postdose
Primary	PK of Glyburide: Cmax		Treatment Period 1 (Days 1-4) and Treatment Period 2 (Days 11-14): predose, up to 72 hours postdose
Primary	PK of Glyburide: Tmax		Treatment Period 1 (Days 1-4) and Treatment Period 2 (Days 11-14): predose, up to 72 hours postdose
Primary	PK of Glyburide: t1/2		Treatment Period 1 (Days 1-4) and Treatment Period 2 (Days 11-14): predose, up to 72 hours postdose
Primary	PK of Digoxin: AUC0-t		Treatment Period 1 (Days 23-30) and Treatment Period 2 (Days 35-42): predose, up to 168 hours postdose
Primary	PK of Digoxin: AUC0-inf		Treatment Period 1 (Days 23-30) and Treatment Period 2 (Days 35-42): predose, up to 168 hours postdose
Primary	PK of Digoxin: Cmax		Treatment Period 1 (Days 23-30) and Treatment Period 2 (Days 35-42): predose, up to 168 hours postdose
Primary	PK of Digoxin: Tmax		Treatment Period 1 (Days 23-30) and Treatment Period 2 (Days 35-42): predose, up to 168 hours postdose
Primary	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	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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