Drug-Drug Interaction Study of TAK-788 and Midazolam in Participants With Advanced Non-small Cell Lung Cancer (NSCLC)

NCT04051827 | Completed Phase 1 Results FDA Drug

• 3 other identifiers: TAK-788-10042019-000725-44U1111-1225-0210
• Study Type: interventional
• Target: 26
• Locations: 3 countries
• Sites: 8

Brief Summary

The purpose of this study is to characterize the effect of repeated oral administration of TAK-788 160 milligram (mg) once daily on the single oral and intravenous dose pharmacokinetics (PK) of midazolam.

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (6)

• Part A, Cmax: Geometric Mean Maximum Observed Plasma Concentration (Cmax) for Midazolam Administered Orally With Mobocertinib (Cycle 1 Day 24) and Without Mobocertinib (Cycle 1 Day 1)

  As planned, this pharmacokinetic (PK) outcome measure was only assessed in Part A.

  Cycle 1: Days 1 and 24 pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length is equal to [=] 30 days)

• Part A, AUC∞: Geometric Mean Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Midazolam Administered Orally With Mobocertinib (Cycle 1 Day 24) and Without Mobocertinib (Cycle 1 Day 1)

  As planned, this PK outcome measure was only assessed in Part A.

  Cycle 1: Days 1 and 24 pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length = 30 days)

• Part A, Cmax: Geometric Mean Maximum Observed Plasma Concentration (Cmax) for Midazolam Administered Intravenously With Mobocertinib (Cycle 1 Day 25) and Without Mobocertinib (Cycle 1 Day 2)

  As planned, this PK outcome measure was only assessed in Part A.

  Cycle 1: Days 2 and 25 pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length = 30 days)

• Part A, AUC∞: Geometric Mean Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Midazolam Administered Intravenously With Mobocertinib (Cycle 1 Day 25) and Without Mobocertinib (Cycle 1 Day 2)

  As planned, this PK outcome measure was only assessed in Part A.

  Cycle 1: Days 2 and 25 pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length = 30 days)

• Part A, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Midazolam Administered Orally With Mobocertinib (Cycle 1 Day 24) and Without Mobocertinib (Cycle 1 Day 1)

  As planned, this PK outcome measure was only assessed in Part A for midazolam 3 mg oral solution.

  Cycle 1: Days 1 and 24 pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length = 30 days)

• Part A, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Midazolam Administered Intravenously With Mobocertinib (Cycle 1 Day 25) and Without Mobocertinib (Cycle 1 Day 2)

  As planned, this PK outcome measure was only assessed in Part A for midazolam 1 mg intravenous infusion.

  Cycle 1: Days 2 and 25 pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length = 30 days)

Secondary Outcomes (3)

• Part A and B: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)

  Part A:From Day 1 up to 30 days after the last dose of study drug in Cycle 1 (up to 2 months);Part B:From Day 1 of Cycle 2 up to 30 days after the last dose of study drug in Cycle 19 (up to Month 19) (Cycle length, Part A= 30 days; Part B=28 days)

• Part A and B: Number of Participants With Clinically Significant Change From Baseline in Laboratory Values

  Part A: Day 1 of Cycle 1; Part B: Day 1 of every Cycle (Cycle 2 to Cycle 19) (Cycle length, Part A=30 days; Part B =28 days)

• Part A and B: Number of Participants With Clinically Significant Change From Baseline in Vital Signs

  Part A: Day 1 up to Day 26 in Cycle 1; Part B: Day 1 of every Cycle (Cycle 2 to Cycle 19) (Cycle length, Part A=30 days; Part B =28 days)

Study Arms (2)

Part A: Midazolam + TAK-788

EXPERIMENTAL

Midazolam 3 mg, solution, orally, once on Days 1 and 24 and midazolam 1 mg, infusion, intravenously, once on Days 2 and 25 along with TAK-788 160 mg, capsule, orally, once daily from Day 3 through 30 in Cycle 1.

Drug: Midazolam; Drug: TAK-788

Part B: TAK-788

EXPERIMENTAL

TAK-788 160 mg, capsules, orally, once daily in a 28-day treatment cycle from Cycle 2 to Cycle 24, or until progressive disease (PD), intolerable toxicity, or another discontinuation criterion is met, whichever is sooner. Eligible participants from Part A may enter into Part B. Based on the investigator's opinion, if a participant continues to experience clinical benefit, treatment with TAK-788 may be continued after PD.

Drug: TAK-788

Interventions

Midazolam DRUG

Midazolam Oral Solution and Midazolam Intravenous Infusion.

Part A: Midazolam + TAK-788

TAK-788 DRUG

TAK-788 Oral Capsules.

Also known as: AP32788

Part A: Midazolam + TAK-788; Part B: TAK-788

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed locally advanced NSCLC in which the participant is not a candidate for definitive therapy; or, the participant has recurrent or metastatic (Stage IV) disease.
• Refractory or intolerant to standard available therapies.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.
• Minimum life expectancy of 3 months or more.
• Adequate organ function as defined by the following criteria:
• Total serum bilirubin less than or equal to (\<=) 1.5\*upper limit of normal (ULN) (\<=3\*ULN for participants with Gilbert syndrome or if liver function abnormalities are due to underlying malignancy)
• Alanine aminotransferase and aspartate aminotransferase \<=2.5\*ULN (or \<=5\*ULN if liver function abnormalities are due to underlying malignancy)
• Estimated creatinine clearance greater than or equal to (\>=) 30 milliliter per minute (mL/min) (calculated by using the Cockcroft-Gault equation)
• Serum albumin \>= 2 gram/deciliter (g/dL)
• Serum lipase/amylase \<=1.5\*ULN; and
• Serum amylase \<=1.5\*ULN unless the increased serum amylase is due to salivary isoenzymes.
• Adequate bone marrow function as defined by the following criteria:
• Absolute neutrophil count \>=1.5\*10\^9 per liter (/L)
• Platelet count \>=75\*10\^9/L; and
• Hemoglobin \>=9.0 g/dL.

You may not qualify if:

• Received a strong or moderate cytochrome P450 3A (CYP3A) inhibitor or strong or moderate CYP3A inducer within 2 weeks prior to the first dose of TAK-788.
• Received small-molecule anticancer therapy (including but not limited to cytotoxic chemotherapy and investigational agents) within 2 weeks prior to the first dose of TAK-788.
• Received antineoplastic monoclonal antibodies including check point inhibitors within 28 days of the first dose of TAK-788.
• Received radiotherapy \<=14 days prior to the first dose of TAK-788. However, participants are allowed to receive any of the following treatments up to 7 days prior to the first dose: (a) Stereotactic radiosurgery (SRS) (b) stereotactic body radiation therapy (SBRT) or (c) palliative radiation outside the chest and brain.
• Major surgery within 28 days prior to the first dose of TAK-788. Minor surgical procedures, such as catheter placement or minimally invasive biopsy, are allowed.
• Diagnosed with another primary malignancy other than NSCLC except for adequately treated non-melanoma skin cancer or cervical cancer in situ; definitively treated non-metastatic prostate cancer; or another primary malignancy and is definitively relapse-free with at least 3 years elapsed since the diagnosis of the other primary malignancy.
• Have known active brain metastases (have either previously untreated intracranial central nervous system (CNS) metastases or previously treated intracranial CNS metastases with radiologically documented new or progressing CNS lesions). Brain metastases are allowed if they have been treated with surgery and/or radiation and have been stable without requiring corticosteroids to control symptoms within 7 days before the first dose of TAK-788, and have no evidence of new or enlarging brain metastases.
• Current spinal cord compression (symptomatic or asymptomatic and detected by radiographic imaging) or leptomeningeal disease (symptomatic or asymptomatic).
• Have uncontrolled hypertension. Participants with hypertension should be under treatment on study entry to control blood pressure.
• Significant, uncontrolled, or active cardiovascular disease, including, but not limited to the following:
• Myocardial infarction within 6 months prior to the first dose of study drug;
• Unstable angina within 6 months prior to the first dose of study drug;
• Congestive heart failure within 6 months prior to the first dose of study drug. Cardiac ejection fraction \<50% by echocardiogram (ECHO) or multiple gated acquisition scan (MUGA);
• History of clinically significant (as determined by the treating physician) atrial arrhythmia;
• Any history of ventricular arrhythmia; or

Sponsors & Collaborators

• Millennium Pharmaceuticals, Inc.: lead

Study Sites (8)

Royal North Shore Hospital

St Leonards, New South Wales, 2065, Australia

Location

Flinders Medical Centre

Bedford Park, South Australia, 5042, Australia

Location

Peninsula and Southeast Oncology

Frankston, Victoria, 3199, Australia

Location

Nucleus Network

Melbourne, Victoria, 3004, Australia

Location

Netherlands Cancer Institute

Amsterdam, North Holland, 1066 CX, Netherlands

Location

Universitair Medisch Centrum Groningen

Groningen, 9700 RB, Netherlands

Location

The National University Cancer Institute - Singapore

Singapore, 119074, Singapore

Location

Raffles Hospital

Singapore, 188770, Singapore

Location

Related Links

• To obtain more information about this study, click this link.

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

Midazolam; mobocertinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Study Director
• Organization: Takeda

TrialDisclosures@takeda.com

+1-877-825-3327

Study Officials

• Study 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: August 5, 2019
• First Posted: August 9, 2019
• Study Start: December 23, 2019
• Primary Completion: December 17, 2020
• Study Completion: December 7, 2021
• Last Updated: July 28, 2025
• Results First Posted: April 12, 2024

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

AU (4); NL (2); SG (2)