Carcinoma, Non-Small-Cell Lung, Lung Neoplasms
Conditions
Keywords
Drug therapy
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.
Detailed description
The drug being tested in this study is called TAK-788. The study will characterize the effect of repeated oral administration of TAK-788 160 mg on the single oral- and intravenous-dose PK of midazolam, and will assess the safety and tolerability of TAK-788 in participants with advanced NSCLC. The study will enroll approximately 26 participants. The study will be conducted in 2 parts: Part A (Cycle 1: PK Cycle) and Part B (Cycle 2 to Cycle 24: Treatment Cycles). In Part A, participants will receive midazolam as an oral dose and intravenous infusion, along with oral dose of TAK-788 in a single 30-day cycle. After completion of Part A, eligible participants may enter Part B. In Part B, participants will continue to receive oral dose of TAK-788 that they were receiving and tolerating at the end of Part A in a 28-day treatment cycle for up to 23 cycles of treatment, or until progressive disease (PD), intolerable toxicity, or another discontinuation criterion is met. Based on the opinion of investigator, if a participant continue to experience clinical benefit, treatment with TAK-788 may be continued after PD. This multi-center trial will be conducted in Australia, Singapore and the Netherlands. The overall time to participate in this study is 3 years. Participants will make multiple visits to the clinic and will be followed up for 30 days after the last dose of study drug for a follow-up assessment.
Interventions
DRUGMidazolam
Midazolam Oral Solution and Midazolam Intravenous Infusion.
DRUGTAK-788
TAK-788 Oral Capsules.
Sponsors
Millennium Pharmaceuticals, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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).
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Cycle 1: Days 2 and 25 pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length = 30 days) | As planned, this PK outcome measure was only assessed in Part A for midazolam 1 mg intravenous infusion. |
| 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) | Cycle 1: Days 2 and 25 pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length = 30 days) | As planned, this PK outcome measure was only assessed in Part A. |
| 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) | Cycle 1: Days 2 and 25 pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length = 30 days) | As planned, this PK outcome measure was only assessed in Part A. |
| 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) | Cycle 1: Days 1 and 24 pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length = 30 days) | As planned, this PK outcome measure was only assessed in Part A for midazolam 3 mg oral solution. |
| 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) | 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) | As planned, this pharmacokinetic (PK) outcome measure was only assessed in Part A. |
| 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) | Cycle 1: Days 1 and 24 pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length = 30 days) | As planned, this PK outcome measure was only assessed in Part A. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | The clinically significant change from baseline in laboratory values was assessed by the investigator. |
| 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) | — |
| 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) | — |
Countries
Australia, Netherlands, Singapore
Participant flow
Recruitment details
Participants took part in the study at 7 investigative sites in Australia, Singapore, and Netherlands from 23 December 2019 to 07 December 2021.
Pre-assignment details
Participants with a historical diagnosis of locally advanced or metastatic non-small cell lung cancer (NSCLC) were enrolled in this 2-part study to receive midazolam oral solution along with mobocertinib (formerly TAK-788) capsule in Part A (Cycle 1) and mobocertinib capsule only in Part B (Cycle 2 to 19). After completion of Part A, eligible participants entered Part B to continue treatment with mobocertinib. As planned, combined safety data for Parts A and B was collected and reported.
Participants by arm
| Arm | Count |
|---|---|
| Parts A and B: Midazolam + Mobocertinib 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 mobocertinib 160 mg, capsule, orally, once daily from Day 3 through Day 30 in Cycle 1 (Month 1) in Part A. After completion of Part A, eligible participants continued treatment with mobocertinib in Part B to receive mobocertinib 160 mg, capsule, orally, once daily in a 28-day treatment cycle from Cycle 2 to Cycle 19 (Month 18). | 26 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
| Overall Study | Other | 4 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Progressive disease | 16 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Parts A and B: Midazolam + Mobocertinib |
|---|---|
| Age, Continuous | 61.7 years STANDARD_DEVIATION 14.62 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 9 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 17 Participants |
| Region of Enrollment Australia | 14 Participants |
| Region of Enrollment Netherlands | 5 Participants |
| Region of Enrollment Singapore | 7 Participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 4 / 26 |
| other Total, other adverse events | 26 / 26 |
| serious Total, serious adverse events | 20 / 26 |
Outcome results
Primary
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.
Time frame: Cycle 1: Days 2 and 25 pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length = 30 days)
Population: PK evaluable population. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Midazolam Alone | 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) | 90.4 ng*h/mL | Geometric Coefficient of Variation 113 |
| Part A: Midazolam + Mobocertinib | 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) | 71.6 ng*h/mL | Geometric Coefficient of Variation 96 |
Comparison: The ratios of geometric mean midazolam AUC∞ (in the presence vs absence of mobocertinib) and the associated 2-sided 90% CIs were calculated on the basis of the within-patient variance using a mixed-effects ANOVA model fitting terms for treatment (midazolam in the absence and presence of mobocertinib).90% CI: [0.673, 1.04]
Primary
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.
Time frame: Cycle 1: Days 1 and 24 pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length = 30 days)
Population: PK evaluable population. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Midazolam Alone | 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) | 58.3 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 61 |
| Part A: Midazolam + Mobocertinib | 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) | 39.0 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 61.4 |
Comparison: The ratios of geometric mean midazolam AUC∞ (in the presence vs absence of mobocertinib) and the associated 2-sided 90% CIs were calculated on the basis of the within-patient variance using a mixed-effects ANOVA model fitting terms for treatment (midazolam in the absence and presence of mobocertinib).90% CI: [0.532, 0.859]
Primary
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.
Time frame: Cycle 1: Days 2 and 25 pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length = 30 days)
Population: PK evaluable population (Part A, Cycle 1) received protocol-specified dosing regimen without dose reductions prior to Day 26; had no dose interruptions within 1 week prior to Day 24; experienced no more than 1 day of dose interruption within first 14 days of mobocertinib; did not receive excluded concomitant medications through Day 26; and had sufficient midazolam concentration-time data to permit reliable estimation of PK parameters by noncompartmental analysis methods.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Midazolam Alone | 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) | 70.8 ng/mL | Geometric Coefficient of Variation 151 |
| Part A: Midazolam + Mobocertinib | 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) | 92.2 ng/mL | Geometric Coefficient of Variation 132 |
Comparison: The ratios of geometric mean midazolam Cmax (in the presence vs absence of mobocertinib) and the associated 2-sided 90% CIs were calculated on the basis of the within-patient variance using a mixed-effects ANOVA model fitting terms for treatment (midazolam in the absence and presence of mobocertinib).90% CI: [0.886, 1.92]
Primary
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.
Time frame: 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)
Population: Pharmacokinetic (PK) evaluable population (Part A, Cycle 1) received protocol-specified dosing regimen without dose reductions prior to Day 26; had no dose interruptions within 1 week prior to Day 24; experienced no more than 1 day of dose interruption within first 14 days of mobocertinib; did not receive excluded concomitant medications through Day 26; and had sufficient midazolam concentration-time data to permit reliable estimation of PK parameters by noncompartmental analysis methods.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Midazolam Alone | 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) | 17.0 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 60.2 |
| Part A: Midazolam + Mobocertinib | 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) | 17.5 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 60.7 |
Comparison: The ratios of geometric mean midazolam Cmax (in the presence vs absence of mobocertinib) and the associated 2-sided 90 percent (%) confidence intervals (CIs) were calculated on the basis of the within-patient variance using a mixed-effects analysis of variance (ANOVA) model fitting terms for treatment (midazolam in the absence and presence of mobocertinib).90% CI: [0.739, 1.42]
Primary
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.
Time frame: Cycle 1: Days 2 and 25 pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length = 30 days)
Population: PK evaluable population (Part A, Cycle 1) received protocol-specified dosing regimen without dose reductions prior to Day 26; had no dose interruptions within 1 week prior to Day 24; experienced no more than 1 day of dose interruption within first 14 days of mobocertinib; did not receive excluded concomitant medications till completion of PK sampling (Day 26); and had sufficient midazolam concentration-time data to permit reliable estimation of PK parameters by noncompartmental analysis methods.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Midazolam Alone | 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) | 0.0500 hour |
| Part A: Midazolam + Mobocertinib | 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) | 0.0500 hour |
Primary
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.
Time frame: Cycle 1: Days 1 and 24 pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length = 30 days)
Population: PK evaluable population (Part A, Cycle 1) received protocol-specified dosing regimen without dose reductions prior to Day 26; had no dose interruptions within 1 week prior to Day 24; experienced no more than 1 day of dose interruption within first 14 days of mobocertinib; did not receive excluded concomitant medications till completion of PK sampling (Day 26); and had sufficient midazolam concentration-time data to permit reliable estimation of PK parameters by noncompartmental analysis methods.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Midazolam Alone | 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) | 0.517 hour |
| Part A: Midazolam + Mobocertinib | 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) | 0.533 hour |
Secondary
Part A and B: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
Time frame: 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)
Population: The safety population was defined as all participants who received at least 1 dose of any study drug (mobocertinib or midazolam). Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Midazolam Alone | Part A and B: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | 26 Participants |
Secondary
Part A and B: Number of Participants With Clinically Significant Change From Baseline in Laboratory Values
The clinically significant change from baseline in laboratory values was assessed by the investigator.
Time frame: 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)
Population: The safety population was defined as all participants who received at least 1 dose of any study drug (mobocertinib or midazolam). Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Midazolam Alone | Part A and B: Number of Participants With Clinically Significant Change From Baseline in Laboratory Values | Blood creatinine increased | 7 Participants |
| Part A: Midazolam Alone | Part A and B: Number of Participants With Clinically Significant Change From Baseline in Laboratory Values | Amylase increased | 3 Participants |
| Part A: Midazolam Alone | Part A and B: Number of Participants With Clinically Significant Change From Baseline in Laboratory Values | Lipase increased | 3 Participants |
Secondary
Part A and B: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Time frame: 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)
Population: The safety population was defined as all participants who received at least 1 dose of any study drug (mobocertinib or midazolam). Since treatment with mobocertinib was intended to continue without any modification from Part A into Part B, therefore it was planned to analyze the combined safety data (Parts A and B).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Midazolam Alone | Part A and B: Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 Participants |