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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04051827




Registration number
NCT04051827
Ethics application status
Date submitted
5/08/2019
Date registered
9/08/2019

Titles & IDs
Public title
Drug-Drug Interaction Study of TAK-788 and Midazolam in Participants With Advanced Non-small Cell Lung Cancer (NSCLC)
Scientific title
A Phase 1, Open-Label, Multicenter, Drug-Drug Interaction Study of TAK-788 and Midazolam, a Sensitive CYP3A Substrate, in Patients With Advanced Non-Small Cell Lung Cancer
Secondary ID [1] 0 0
2019-000725-44
Secondary ID [2] 0 0
TAK-788-1004
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Carcinoma, Non-Small-Cell Lung 0 0
Lung Neoplasms 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Midazolam
Treatment: Drugs - TAK-788

Experimental: Part A: Midazolam + TAK-788 - 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.

Experimental: Part B: TAK-788 - 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.


Treatment: Drugs: Midazolam
Midazolam Oral Solution and Midazolam Intravenous Infusion.

Treatment: Drugs: TAK-788
TAK-788 Oral Capsules.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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)
Timepoint [1] 0 0
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)
Primary outcome [2] 0 0
Part A, AUC8: 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)
Timepoint [2] 0 0
Cycle 1: Days 1 and 24 pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length = 30 days)
Primary outcome [3] 0 0
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)
Timepoint [3] 0 0
Cycle 1: Days 2 and 25 pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length = 30 days)
Primary outcome [4] 0 0
Part A, AUC8: 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)
Timepoint [4] 0 0
Cycle 1: Days 2 and 25 pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length = 30 days)
Primary outcome [5] 0 0
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)
Timepoint [5] 0 0
Cycle 1: Days 1 and 24 pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length = 30 days)
Primary outcome [6] 0 0
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)
Timepoint [6] 0 0
Cycle 1: Days 2 and 25 pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length = 30 days)
Secondary outcome [1] 0 0
Part A and B: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
Timepoint [1] 0 0
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)
Secondary outcome [2] 0 0
Part A and B: Number of Participants With Clinically Significant Change From Baseline in Laboratory Values
Timepoint [2] 0 0
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)
Secondary outcome [3] 0 0
Part A and B: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Timepoint [3] 0 0
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)

Eligibility
Key inclusion criteria
1. 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.
2. Refractory or intolerant to standard available therapies.
3. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.
4. Minimum life expectancy of 3 months or more.
5. 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.
6. 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.
7. Normal QT interval on screening electrocardiogram (ECG), defined as QT interval with Fridericia's correction (QTcF) of <= 450 millisecond (msec) in males or <= 470 msec in females. (as conducted and interpreted in accordance to local institutional practices and confirmed by principal investigator [PI]).
8. All toxicities from prior anticancer therapy must have resolved to <= Grade 1 according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 or have resolved to baseline, at the time of first dose of TAK-788. Note: treatment-related Grade 2 or 3 alopecia and treatment-related Grade 2 peripheral neuropathy are allowed if deemed irreversible.
9. Suitable venous access for study-required blood sampling (that is, including for PK, pharmacodynamics, and clinical laboratory tests).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. 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.
2. 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.
3. Received antineoplastic monoclonal antibodies including check point inhibitors within 28 days of the first dose of TAK-788.
4. 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.
5. 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.
6. 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.
7. 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.
8. Current spinal cord compression (symptomatic or asymptomatic and detected by radiographic imaging) or leptomeningeal disease (symptomatic or asymptomatic).
9. Have uncontrolled hypertension. Participants with hypertension should be under treatment on study entry to control blood pressure.
10. 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
* Cerebrovascular accident or transient ischemic attack within 6 months prior to the first dose of study drug.
11. Treatment with medications known to be associated with the development of torsades de pointes.
12. Gastrointestinal illness or disorder that could affect oral absorption of TAK-788 or midazolam.

Study design
Purpose of the study
Other
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
23/12/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
7/12/2021
Sample size
Target
Accrual to date
Final
26
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [2] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [3] 0 0
Peninsula and Southeast Oncology - Frankston
Recruitment hospital [4] 0 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 0 0
2065 - St Leonards
Recruitment postcode(s) [2] 0 0
5042 - Bedford Park
Recruitment postcode(s) [3] 0 0
3199 - Frankston
Recruitment postcode(s) [4] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
Netherlands
State/province [1] 0 0
Noord-holland
Country [2] 0 0
Netherlands
State/province [2] 0 0
Groningen
Country [3] 0 0
Singapore
State/province [3] 0 0
Singapore

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Millennium Pharmaceuticals, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Study Director
Address 0 0
Millennium Pharmaceuticals, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
Available to whom?
IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://vivli.org/ourmember/takeda/


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT04051827