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

NCT03928327 | Completed Phase 1 Results FDA Drug

• 1 other identifier: TAK-788-1006
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteers

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (7)

• Treatment B vs Treatment A (Part 1), Combined Molar Exposure for Cmax: Maximum Observed Plasma Concentration of TAK-788, AP32960, and AP32914

  The combined molar exposure Cmax for TAK-788 and its metabolites AP32960 and AP3914 value was calculated as the sum of each molar Cmax which was multiplied by 1000 and divided by molecular weight of each analyte, TAK-788, AP32960, and AP32914 respectively. The combined molar exposure was presented in nanomolar.

  Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose

• Treatment D Vs Treatment C (Part 2), Combined Molar Exposure for Cmax: Maximum Observed Plasma Concentration of TAK-788, AP32960, and AP32914

  The combined molar exposure Cmax for TAK-788 and its metabolites AP32960 and AP3914 value was calculated as the sum of each molar Cmax which was multiplied by 1000 and divided by molecular weight of each analyte, TAK-788, AP32960, and AP32914 respectively. The combined molar exposure was presented in nanomolar.

  Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

• Treatment B Vs Treatment A (Part 1), Combined Molar Exposure for AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity, Calculated Using the Observed Value of the Last Quantifiable Concentration of TAK-788, AP32960, and AP32914

  The combined molar exposure AUC∞ for TAK-788 and its metabolites AP32960 and AP3914 value was calculated as the sum of each molar AUC∞ which was multiplied by 1000 and divided by molecular weight of each analyte, TAK-788, AP32960, and AP32914 respectively. The combined molar exposure was presented in hour\*nanomolar.

  Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose

• Treatment D Vs Treatment C (Part 2), Combined Molar Exposure for AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity, Calculated Using the Observed Value of the Last Quantifiable Concentration of TAK-788, AP32960, and AP32914

  The combined molar exposure AUC∞ for TAK-788 and its metabolites AP32960 and AP3914 value was calculated as the sum of each molar AUC∞ which was multiplied by 1000 and divided by molecular weight of each analyte, TAK-788, AP32960, and AP32914 respectively. The combined molar exposure was presented in hour\*nanomolar.

  Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

• Tmax - Time to Reach the Maximum Plasma Concentration (Cmax) of TAK-788

  Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose

• Tmax - Time to Reach the Maximum Plasma Concentration (Cmax) of AP32960

  Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose

• Tmax - Time to Reach the Maximum Plasma Concentration (Cmax) of AP32914

  Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose

Study Arms (2)

Part 1, Treatment Sequence AB

EXPERIMENTAL

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.

Drug: TAK-788; Drug: Itraconazole

Part 2, Treatment Sequence CD

EXPERIMENTAL

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.

Drug: TAK-788; Drug: Rifampin

Interventions

TAK-788 DRUG

TAK-788 Capsules

Also known as: Mobocertinib

Part 1, Treatment Sequence AB; Part 2, Treatment Sequence CD

Itraconazole DRUG

Itraconazole Oral solution

Part 1, Treatment Sequence AB

Rifampin DRUG

Rifampin Capsules

Part 2, Treatment Sequence CD

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• History or presence of alcoholism or drug abuse within the past 2 years prior to the first dosing.
• History or presence of hypersensitivity or idiosyncratic reaction to the study drugs or related compounds.
• Presence of an acute lung infection, within 3 months of screening.
• History or presence of any previous lung disease.
• 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.
• Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV).
• Seated blood pressure is less than 90/40 mmHg or greater than 140/90 mmHg at screening.
• Seated heart rate is lower than 40 bpm or higher than 99 bpm at screening.
• 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.
• Estimated creatinine clearance \<90 mL/min at screening
• 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.

Sponsors & Collaborators

• Millennium Pharmaceuticals, Inc.: lead

Study Sites (1)

Celerion

Tempe, Arizona, 85283, United States

Location

Related Publications (1)

• 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.

  PMID: 34145979 DERIVED

MeSH Terms

Interventions

mobocertinib; Itraconazole; Rifampin

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Medical director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director

  Millennium Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: April 24, 2019
• First Posted: April 26, 2019
• Study Start: May 2, 2019
• Primary Completion: August 16, 2019
• Study Completion: August 16, 2019
• Last Updated: August 21, 2020
• Results First Posted: August 21, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will share

Locations

US (1)