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

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

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 Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Microgestin®; Drug: IW-3718; Drug: Levothyroxine; Drug: Glyburide; Drug: Digoxin

• Study Type: Interventional
• Enrollment (Actual): 87
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78744
      • PPD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Healthy Volunteers; 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).	Drug: Microgestin®; 30 μg/1500 μg tablets for oral administration; Other Names: ethinyl estradiol 30 μg and norethindrone 1500 μg; Drug: IW-3718; 500-mg film-coated tablets for oral administration
Experimental: Part 2: Healthy Volunteers; 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).	Drug: IW-3718; 500-mg film-coated tablets for oral administration; Drug: Levothyroxine; 600 μg tablets for oral administration
Experimental: Part 3: Healthy Volunteers; 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).	Drug: IW-3718; 500-mg film-coated tablets for oral administration; Drug: Glyburide; 5 mg tablets for oral administration; Drug: Digoxin; 0.25 mg tablets for oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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: Maximum Observed Plasma Concentration (Cmax)	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

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Ironwood Pharmaceuticals, Inc.
• Investigators: Study Director: Zurab Machaidze, MD, Ironwood Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2019
• Primary Completion (Actual): June 25, 2019
• Study Completion (Actual): July 3, 2019

Study Registration Dates

• First Submitted: February 26, 2019
• First Submitted That Met QC Criteria: February 26, 2019
• First Posted (Actual): February 27, 2019

Study Record Updates

• Last Update Posted (Actual): July 29, 2019
• Last Update Submitted That Met QC Criteria: July 26, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protective Agents; Estrogens; Cardiotonic Agents; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral, Hormonal; Digoxin; Estradiol; Ethinyl Estradiol; Norethindrone; Glyburide
• Other Study ID Numbers: C3718-103

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No