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

NCT03856970 | Completed Phase 1 FDA Drug

• 1 other identifier: C3718-103
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (20)

• 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 Outcomes (5)

• 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

Study Arms (3)

Part 1: Healthy Volunteers

EXPERIMENTAL

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®; Drug: IW-3718

Part 2: Healthy Volunteers

EXPERIMENTAL

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: Levothyroxine; Drug: IW-3718

Part 3: Healthy Volunteers

EXPERIMENTAL

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: Glyburide; Drug: Digoxin; Drug: IW-3718

Interventions

Microgestin® DRUG

30 μg/1500 μg tablets for oral administration

Also known as: ethinyl estradiol 30 μg and norethindrone 1500 μg

Part 1: Healthy Volunteers

Levothyroxine DRUG

600 μg tablets for oral administration

Part 2: Healthy Volunteers

Glyburide DRUG

5 mg tablets for oral administration

Part 3: Healthy Volunteers

Digoxin DRUG

0.25 mg tablets for oral administration

Part 3: Healthy Volunteers

IW-3718 DRUG

500-mg film-coated tablets for oral administration

Part 1: Healthy Volunteers; Part 2: Healthy Volunteers; Part 3: Healthy Volunteers

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ironwood Pharmaceuticals, Inc.: lead

Study Sites (1)

PPD

Austin, Texas, 78744, United States

Location

MeSH Terms

Interventions

Ethinyl Estradiol; Norethindrone; Thyroxine; Glyburide; Digoxin

Intervention Hierarchy (Ancestors)

Norpregnatrienes; Norpregnanes; Norsteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estrogenic Steroids, Alkylated; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Norpregnenes; Thyroid Hormones; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Sulfonylurea Compounds; Urea; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Glycosides; Carbohydrates

Study Officials

• Zurab Machaidze, MD

  Ironwood Pharmaceuticals, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2019
• First Posted: February 27, 2019
• Study Start: March 11, 2019
• Primary Completion: June 25, 2019
• Study Completion: July 3, 2019
• Last Updated: July 29, 2019

Record last verified: 2019-07

Locations

US (1)