Who is sponsoring NCT03420742?

NCT03420742 is sponsored by Takeda.

What drugs are being tested in NCT03420742?

Interventions in NCT03420742: Midazolam, Brigatinib.

Is NCT03420742 still recruiting?

NCT03420742 is currently completed. Last updated 27 January 2023.

Are results published for NCT03420742?

Yes — primary outcome results have been posted to ClinicalTrials.gov. See the outcomes section above for details.

Last reviewed 2023-01-27 · How we verify

NCT03420742

Name: Drug Landscape Pharmaceutical Database
Creator: Drug Landscape
Published: 2026-01-01
License: https://creativecommons.org/licenses/by/4.0/

A Phase 1 Drug-Drug Interaction Study Between Brigatinib and the CYP3A Substrate, Midazolam, in Participants With ALK-Positive or ROS1-Positive Solid Tumors

Completed Phase 1 Results posted Last updated 27 January 2023

What this trial tests

Phase 1 trial testing Midazolam in Carcinoma, Advanced ALK+ or ROS1+Non-Small-Cell Lung, Neoplasm, Advanced ALK+ or ROS1+Solid Tumors in 24 participants. Completed in 29 April 2021.

Timeline

26 June 2019

Primary endpoint
24 March 2020

29 April 2021

Quick facts

Lead sponsor	Takeda
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	sequential
Masking	none
Primary purpose	other
Enrollment	24
Start date	26 June 2019
Primary completion	24 March 2020
Estimated completion	29 April 2021
Sites	14 locations across France, Netherlands, Spain, Italy

Drugs / interventions tested

Midazolam (midazolam) — full drug profile →
Brigatinib (brigatinib) — full drug profile →

Conditions studied

Carcinoma, Advanced ALK+ or ROS1+Non-Small-Cell Lung, Neoplasm, Advanced ALK+ or ROS1+Solid Tumors — all drugs for Carcinoma, Advanced ALK+ or ROS1+Non-Small-Cell Lung, Neoplasm, Advanced ALK+ or ROS1+Solid Tumors →

Sponsor

Takeda — full company profile →

Who can join

18 and older, any sex, with Carcinoma, Advanced ALK+ or ROS1+Non-Small-Cell Lung, Neoplasm, Advanced ALK+ or ROS1+Solid Tumors. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Part A, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Midazolam Primary · Cycle 1, Days 1 (Midazolam alone) and 21 (Midazolam + Brigatinib): pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length is 28 days)

The statistical analysis was calculated via a mixed-effects analysis of variance (ANOVA) fitting terms for treatment (midazolam with or without brigatinib coadministration).

Group	Value	95% CI
Part A, Cycle 1 Day 1: Midazolam Alone	57.2	± 30.3
Part A, Cycle 1 Day 21: Midazolam + Brigatinib	42.1	± 54.2

Part A, Cmax: Maximum Observed Plasma Concentration for Midazolam Primary · Cycle 1, Days 1 (Midazolam alone) and 21 (Midazolam + Brigatinib): pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length is 28 days)

The statistical analysis was calculated via a mixed-effects ANOVA fitting terms for treatment (midazolam with or without brigatinib coadministration).

Group	Value	95% CI
Part A, Cycle 1 Day 1: Midazolam Alone	19.7	± 42.6
Part A, Cycle 1 Day 21: Midazolam + Brigatinib	16.5	± 49.9

Part A, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Midazolam Primary · Cycle 1, Days 1 (Midazolam alone) and 21 (Midazolam + Brigatinib): pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length is 28 days)

Group	Value	95% CI
Part A, Cycle 1 Day 1: Midazolam Alone	0.500	0.220 – 1.93
Part A, Cycle 1 Day 21: Midazolam + Brigatinib	0.500	0.250 – 1.00

Adverse events — posted to ClinicalTrials.gov

Time frame: Treatment-emergent adverse events were adverse events (AEs) that started from the first dose of the study drug up to 30 days after the last dose of the study drug (up to Cycle 20 Day 30 ) (Cycle length =28 days). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Parts A and B: All Participants

Serious: 17/24 (71%)

Deaths: 8/24

Serious adverse events (18 terms)

Reaction	System	Parts A and B: All Partici…
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—
Non-small cell lung cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—
Disease progression	General disorders	—
Pneumonia	Infections and infestations	—
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—
Bile duct obstruction	Hepatobiliary disorders	—
COVID-19	Infections and infestations	—
Confusional state	Psychiatric disorders	—
Haematuria	Renal and urinary disorders	—
Infection	Infections and infestations	—
Invasive ductal breast carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—
Malignant neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—
Metastases to liver	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—
Neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—
Ovarian cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—
Pancreatitis	Gastrointestinal disorders	—
Pneumothorax	Respiratory, thoracic and mediastinal disorders	—
Respiratory tract infection	Infections and infestations	—

Other adverse events (30 terms — click to expand)

Reaction	System	Parts A and B: All Partici…
Blood creatine phosphokinase increased	Investigations	—
Nausea	Gastrointestinal disorders	—
Diarrhoea	Gastrointestinal disorders	—
Aspartate aminotransferase increased	Investigations	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—
Alanine aminotransferase increased	Investigations	—
Anaemia	Blood and lymphatic system disorders	—
Vomiting	Gastrointestinal disorders	—
Cough	Respiratory, thoracic and mediastinal disorders	—
Lipase increased	Investigations	—
Amylase increased	Investigations	—
Decreased appetite	Metabolism and nutrition disorders	—
Hypertension	Vascular disorders	—
Pyrexia	General disorders	—
Blood cholesterol increased	Investigations	—
Fatigue	General disorders	—
Abdominal pain	Gastrointestinal disorders	—
Asthenia	General disorders	—
Blood alkaline phosphatase increased	Investigations	—
Headache	Nervous system disorders	—
Urinary tract infection	Infections and infestations	—
Blood lactate dehydrogenase increased	Investigations	—
Chills	General disorders	—
Constipation	Gastrointestinal disorders	—
Dizziness	Nervous system disorders	—
Dry mouth	Gastrointestinal disorders	—
Hypomagnesaemia	Metabolism and nutrition disorders	—
Non-small cell lung cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—
Stomatitis	Gastrointestinal disorders	—
Tachycardia	Cardiac disorders	—

Most-reported serious reactions: Dyspnoea, Non-small cell lung cancer, Disease progression, Pneumonia, Tumour pain, Bile duct obstruction, COVID-19, Confusional state.

Data from ClinicalTrials.gov NCT03420742 adverse events section.

Sponsor's own description

The purpose of this study is to characterize the effect of repeat-dose administration of brigatinib 180 milligram (mg) once daily (QD) on the single-dose pharmacokinetics (PK) of midazolam.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

Safety and efficacy of anaplastic lymphoma kinase tyrosine kinase inhibitors in non‑small cell lung cancer (Review).
Wang L, Wang W. · · 2021 · cited 42× · PMID 33200229 · DOI 10.3892/or.2020.7851
Effects of Strong CYP2C8 or CYP3A Inhibition and CYP3A Induction on the Pharmacokinetics of Brigatinib, an Oral Anaplastic Lymphoma Kinase Inhibitor, in Healthy Volunteers.
Tugnait M, Gupta N, Hanley MJ, Sonnichsen D, et al · · 2020 · cited 20× · PMID 31287236 · DOI 10.1002/cpdd.723

Verify or expand the search:

Other trials of Midazolam

Trials testing the same drug.

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Other Takeda trials

Trials by the same sponsor.

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NCT07293364 — A Study to Learn About the C1-Inhibitor Function as Diagnosis for Hereditary Angioedema · NA · not yet recruiting
NCT07218393 — A Study About the Diagnosis and Management of Hereditary Angioedema (HAE) in Egypt · not yet recruiting
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Verify against primary sources

ClinicalTrials.gov — authoritative US registry record
WHO ICTRP — international registry index
EU Clinical Trials Register
Sponsor press releases (Google)

Data sources for this page

Trial protocol + status: ClinicalTrials.gov NCT03420742 (US National Library of Medicine, public domain)
Publications: Europe PMC API search by NCT ID, retrieved 10 June 2026
Drug + disease cross-links: matched in real time against Drug Landscape's normalised drug + company + condition tables
Sponsor: as reported to ClinicalTrials.gov by Takeda
Last refreshed: 27 January 2023

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03420742.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing