A Study to Evaluate Drug-Drug Interaction of TAK-788 With Itraconazole and Rifampin in Healthy Adult Participants

NCT ID: NCT03928327

Last Updated: 2020-08-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-02
• Study Completion Date: 2019-08-16

Brief Summary

The purpose of this study is to characterize the effect of itraconazole (Part 1) and rifampin (Part 2) on the single-dose pharmacokinetics (PK) of TAK-788 and its active metabolites (AP32960 and AP32914) in healthy adult participants.

Detailed Description

The drug being tested in this study is called TAK-788 (Mobocertinib). The study assessed the drug-drug interaction of TAK-788 with either a strong cytochrome P-450 (CYP)3A inhibitor, itraconazole (Part 1) or with a strong CYP3A inducer, rifampin (Part 2) in healthy adult participants.

The study enrolled 24 healthy participants. The study was designed to consist of 2 parts: Part 1- TAK-788 assessment with itraconazole Part 2- TAK-788 assessment with rifampin. Part 1 had 2 cohorts:

Part 1: Participants (n = 12) received a single oral dose of 20 mg capsule of TAK-788 on Day 1 of Period 1 followed by 200 mg itraconazole oral solution once daily (QD) in Period 2 on Days 1 to Day 14 and a single oral dose of TAK-788 20 mg capsule were coadmistered on Day 5 of Period 2.

In Part 2 participants (n = 12) received a single oral 160 mg dose of TAK-788 capsules in Period 1 of Day 1 followed by 600 mg capsules of rifampin QD in Period 2 Days 1 to Day 13 and a single dose of 160 mg TAK-788 capsules was coadministered on Day 7 of Period 1. There was a washout period of 7 days between the dose of TAK-788 on Period 1 and the first dose of rifampin in Period 2.

This single-center trial was conducted in the United States. The overall time to participate in this study was approximately 120 days (including screening period). Participants were contacted by telephone 30 days after the last dose of study drug for a follow-up assessment.

Conditions

Healthy Volunteers

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Part 1, Treatment Sequence AB

TAK-788 20 mg, capsule, at Hour 0 on Day 1 followed by an overnight fast (Treatment A). Following Treatment A, participants received itraconazole 200 mg solution, orally, once daily (QD) on Days 1 to Day 14 and a single oral dose of TAK-788 20 mg capsule was coadministered on Day 5 (Treatment B). There was a washout period of 7 days between the two treatments.

Group Type: EXPERIMENTAL

TAK-788

Intervention Type: DRUG

TAK-788 Capsules

Itraconazole

Intervention Type: DRUG

Itraconazole Oral solution

Part 2, Treatment Sequence CD

TAK-788 160 mg, orally, at Hour 0 on Day 1 following an overnight fast (Treatment C). Following Treatment C, participants received rifampin 600 mg as capsules, orally, once daily (QD) on Days 1 to 13 and TAK-788 160 mg as capsules, orally was coadministered on Day 7 (Treatment D). There was a washout period of 7 days between the two treatments.

Group Type: EXPERIMENTAL

TAK-788

Intervention Type: DRUG

TAK-788 Capsules

Rifampin

Intervention Type: DRUG

Rifampin Capsules

Interventions

TAK-788

TAK-788 Capsules

Intervention Type: DRUG

Itraconazole

Itraconazole Oral solution

Intervention Type: DRUG

Rifampin

Rifampin Capsules

Intervention Type: DRUG

Other Intervention Names

Mobocertinib

Eligibility Criteria

Inclusion Criteria

1. Continuous non smoker who has not used nicotine containing products for at least 3 months prior to the first dose and throughout the study based on participant self-reporting.

2. Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs, or electrocardiograms (ECGs), as deemed by the Investigator or designee. Has liver function tests (LFTs) including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin within the upper limit of normal at screening and at first check-in.

3. Normal baseline spirometry for forced vital capacity (FVC) and forced expiratory volume (FEV1)/FVC within 7 days prior to the first dosing based on the following normal FVC and FEV1/FVC range: a. 20 - 39 years of age: ≥ 80% and b. 40 - 55 years of age: ≥ 75%

4. Body mass index (BMI) ≥18.0 and ≤32.0 kg/m^2, at screening.

Exclusion Criteria

1. History or presence of alcoholism or drug abuse within the past 2 years prior to the first dosing.

2. History or presence of hypersensitivity or idiosyncratic reaction to the study drugs or related compounds.

3. Presence of an acute lung infection, within 3 months of screening.

4. History or presence of any previous lung disease.

5. Part 1 only: History or presence of any of the following, deemed clinically significant by the PI or designee, and as confirmed by the Sponsor:

• Ventricular dysfunction or risk factors for Torsades de Pointes (e.g., heart failure, cardiomyopathy, family history of Long QT Syndrome);
• Uncorrected hypokalemia (potassium levels <3.7) and/or hypomagnesemia (magnesium levels <1.9);
• Myasthenia gravis.

6. Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV).

7. Seated blood pressure is less than 90/40 mmHg or greater than 140/90 mmHg at screening.

8. Seated heart rate is lower than 40 bpm or higher than 99 bpm at screening.

9. QTcF interval is >460 msec (males) or >470 msec (females) or ECG findings are deemed abnormal with clinical significance by the Investigator or designee at screening.

10. Estimated creatinine clearance <90 mL/min at screening

11. Unable to refrain from or anticipates the use of:

• Any drug, including prescription and non-prescription medications, herbal remedies, or vitamin supplements within 14 days prior to the first dosing and throughout the study. Medication listed as part of acceptable birth control methods will be allowed. Thyroid hormone replacement medication may be permitted if the subject has been on the same stable dose for the immediate 3 months prior to the first dosing. Acetaminophen (up to 2 g per 24 hour period) may be permitted during the study, only after initial dosing.
• Any drugs known to be inhibitors or inducers of CYP3A enzymes and/or P-gp, including St. John's Wort, within 28 days prior to the first dosing and throughout the study. Appropriate sources (e.g., Flockhart Table™) will be consulted to confirm lack of pharmacokinetic (PK)/pharmacodynamics interaction with study drugs.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Millennium Pharmaceuticals, Inc.

Locations

Celerion

Tempe, Arizona, United States

Countries

United States

References

Zhang S, Jin S, Griffin C, Feng Z, Lin J, Venkatakrishnan K, Gupta N. Effects of Itraconazole and Rifampin on the Pharmacokinetics of Mobocertinib (TAK-788), an Oral Epidermal Growth Factor Receptor Inhibitor, in Healthy Volunteers. Clin Pharmacol Drug Dev. 2021 Sep;10(9):1044-1053. doi: 10.1002/cpdd.967. Epub 2021 Jun 19.

Reference Type: DERIVED

PMID: 34145979 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

TAK-788-1006

Identifier Type: -

Identifier Source: org_study_id