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NCT02197247

Study to Assess the Effect of Rifampicin on Blood Levels and Safety of AZD9291, in Patients With EGFRm+ NSCLC

Completed Phase 1 Results posted Last updated 12 July 2021
What this trial tests

Phase 1 trial testing Pharmacokinetic sampling - AZD9291 in Non Small Cell Lung Cancer in 41 participants. Completed in 26 May 2021.

Timeline
4 December 2014
Primary endpoint
9 July 2015
26 May 2021

Quick facts

Lead sponsorAstraZeneca
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Maskingnone
Primary purposeother
Enrollment41
Start date4 December 2014
Primary completion9 July 2015
Estimated completion26 May 2021
Sites18 locations across Netherlands, Taiwan, United Kingdom, South Korea, United States, Spain

Drugs / interventions tested

Conditions studied

Sponsor

AstraZeneca — full company profile →

Who can join

Adults 18 to 130, any sex, with Non Small Cell Lung Cancer. 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.

Assessment of Maximum Plasma Concentration for AZD9291 After Dosing Alone and in Combination With Rifampicin (Css,Max) Primary · Samples collected on Day 28 following AZD9291 alone and Day 49 (following AZD9291 and rifampicin) at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose in Part A.

Rate and extent of absorption of AZD9291 by assessment of maximum plasma concentration at steady state (Css,max). AZD9291 doses were first without, then with rifampicin (Periods 1 and 2, respectively).

GroupValue95% CI
AZD9291 Alone (Period 1)577.4± 44.7
AZD9291 + Rifampicin (Period 2)147.5± 48.2
Assessment of Area Under the Plasma Concentration-time Curve During the Dosing Interval for AZD9291 After Dosing Alone and in Combination With Rifampicin (AUCtau) Primary · Samples collected on Day 28 following AZD9291 alone and Day 49 following AZD9291 and rifampicin at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose in Part A.

Rate and extent of absorption of AZD9291 by assessment of AUCtau. AZD9291 doses were first without, then with rifampicin (Periods 1 and 2, respectively).

GroupValue95% CI
AZD9291 Alone (Period 1)10870± 44.3
AZD9291 + Rifampicin (Period 2)2192± 43.8
Assessment of Css,Max for AZD9291 Before and After Rifampicin Secondary · Samples collected on Day 28 and 77 following AZD9291 alone at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose in Part A.

Rate and extent of absorption of AZD9291 by assessment of Css,max. AZD9291 alone before rifampicin (Period 1) and AZD9291 alone after rifampicin (Period 3).

GroupValue95% CI
AZD9291 Alone (Period 1)577.4± 44.7
AZD9291 Alone (Period 3)531.4± 37.9
Assessment of Css,Max for AZ5104 (Metabolite) Secondary · Samples collected on Day 28 and 77 (following AZD9291 alone) and Day 49 (following AZD9291 and rifampicin) at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose in Part A.

Rate and extent of absorption of AZ5104 (metabolite) by assessment of Css,max. AZD9291 dosing alone and in combination with rifampicin (all periods).

GroupValue95% CI
AZD9291 Alone (Period 1)60.40± 57.2
AZD9291 + Rifampicin (Period 2)12.28± 52.6
AZD9291 Alone (Period 3)50.73± 49.8
Assessment of Css,Max for AZ7550 (Metabolite) Secondary · Samples collected on Day 28 and 77 (following AZD9291 alone) and Day 49 (following AZD9291 and rifampicin) at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose in Part A.

Rate and extent of absorption of AZ7550 (metabolite) by assessment of Css,max. AZD9291 dosing alone and in combination with rifampicin (all periods).

GroupValue95% CI
AZD9291 Alone (Period 1)53.54± 43.7
AZD9291 + Rifampicin (Period 2)73.14± 25.0
AZD9291 Alone (Period 3)53.24± 34.4
Assessment of Css,Max for Rifampicin Secondary · Samples collected on Day 49 (following AZD9291 and rifampicin) at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose in Part A.

Rate and extent of absorption of rifampicin by assessment of Css,max. AZD9291 dosing in combination with rifampicin (Period 2).

GroupValue95% CI
AZD9291 + Rifampicin (Period 2)13810± 40.6
Assessment of AUCtau for AZD9291 Before and After Rifampicin Secondary · Samples collected on Day 28 and 77 following AZD9291 alone at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose in Part A.

Rate and extent of absorption of AZD9291 by assessment of AUCtau. AZD9291 alone before rifampicin (Period 1) and AZD9291 alone after rifampicin (Period 3).

GroupValue95% CI
AZD9291 Alone (Period 1)10870± 44.3
AZD9291 Alone (Period 3)10060± 36.8
Assessment of AUCtau for AZ5104 (Metabolite) Secondary · Samples collected on Day 28 and 77 (following AZD9291 alone) and Day 49 (following AZD9291 and rifampicin) at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose in Part A.

Rate and extent of absorption of AZ5104 (metabolite) by assessment of AUCtau. AZD9291 dosing alone and in combination with rifampicin (all periods).

GroupValue95% CI
AZD9291 Alone (Period 1)1206± 55.8
AZD9291 + Rifampicin (Period 2)210.3± 48.0
AZD9291 Alone (Period 3)1029± 49.7
Assessment of AUCtau for AZ7550 (Metabolite) Secondary · Samples collected on Day 28 and 77 (following AZD9291 alone) and Day 49 (following AZD9291 and rifampicin) at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose in Part A.

Rate and extent of absorption of AZ7550 (metabolite) by assessment of AUCtau. AZD9291 dosing alone and in combination with rifampicin (all periods).

GroupValue95% CI
AZD9291 Alone (Period 1)1107± 41.7
AZD9291 + Rifampicin (Period 2)1416± 25.6
AZD9291 Alone (Period 3)1111± 31.7
Assessment of AUCtau for Rifampicin Secondary · Samples collected on Day 49 (following AZD9291 and rifampicin) at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose in Part A.

Rate and extent of absorption of rifampicin by assessment of AUCtau. AZD9291 dosing in combination with rifampicin (Period 2).

GroupValue95% CI
AZD9291 + Rifampicin (Period 2)58610± 36.8
Assessment of Tss,Max for AZD9291, and AZ5104 and AZ7550 (Metabolites) Secondary · Samples collected on Day 28 and 77 (following AZD9291 alone) and Day 49 (following AZD9291 and rifampicin) at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose in Part A.

Rate and extent of absorption of AZD9291, and AZ5104 and AZ7550 (metabolites) by assessment of time to reach maximum plasma concentration at steady state (tss,max). AZD9291 dosing alone and in combination with rifampicin (all periods).

AZD9291 tss,max
GroupValue95% CI
AZD9291 Alone (Period 1)4.972.88 – 9.88
AZD9291 + Rifampicin (Period 2)5.883.00 – 10.00
AZD9291 Alone (Period 3)6.003.17 – 23.92
AZ5104 tss,max
GroupValue95% CI
AZD9291 Alone (Period 1)6.000.00 – 24.00
AZD9291 + Rifampicin (Period 2)6.033.00 – 11.43
AZD9291 Alone (Period 3)6.000.00 – 24.00
AZ7550 tss,max
GroupValue95% CI
AZD9291 Alone (Period 1)6.142.88 – 24.92
AZD9291 + Rifampicin (Period 2)7.954.00 – 12.00
AZD9291 Alone (Period 3)7.031.10 – 24.00
Assessment of Tss,Max for Rifampicin Secondary · Samples collected on Day 49 (following AZD9291 and rifampicin) at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose in Part A.

Rate and extent of absorption of rifampicin by assessment of tss,max. AZD9291 dosing in combination with rifampicin (Period 2).

GroupValue95% CI
AZD9291 + Rifampicin (Period 2)2.000.83 – 6.07

Adverse events — posted to ClinicalTrials.gov

Time frame: Approximately 3 months for Part A; up to approximately 14 months for Part B and approximately 17 months for Overall (Parts A and B combined).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Overall
Serious: 11/41 (27%)
Deaths: —
Part A
Serious: 7/41 (17%)
Deaths: —
Part B
Serious: 6/34 (18%)
Deaths: —

Serious adverse events (13 terms)

ReactionSystemOverallPart APart B
InfluenzaInfections and infestations———
Atrial fibrillationCardiac disorders———
Cardiac failure congestiveCardiac disorders———
IleusGastrointestinal disorders———
MalaiseGeneral disorders———
Hepatitis BInfections and infestations———
PneumoniaInfections and infestations———
Pulmonary sepsisInfections and infestations———
Femur fractureInjury, poisoning and procedural complications———
HyperkalaemiaMetabolism and nutrition disorders———
Muscular weaknessMusculoskeletal and connective tissue disorders———
Thrombotic strokeNervous system disorders———
ThrombophlebitisVascular disorders———
Other adverse events (57 terms — click to expand)

ReactionSystemOverallPart APart B
DiarrhoeaGastrointestinal disorders———
Decreased appetiteMetabolism and nutrition disorders———
Dry skinSkin and subcutaneous tissue disorders———
NauseaGastrointestinal disorders———
FatigueGeneral disorders———
VomitingGastrointestinal disorders———
Back painMusculoskeletal and connective tissue disorders———
StomatitisGastrointestinal disorders———
CoughRespiratory, thoracic and mediastinal disorders———
Musculoskeletal painMusculoskeletal and connective tissue disorders———
ParonychiaInfections and infestations———
HeadacheNervous system disorders———
ConstipationGastrointestinal disorders———
Oedema peripheralGeneral disorders———
Weight decreasedInvestigations———
AstheniaGeneral disorders———
AnaemiaBlood and lymphatic system disorders———
Upper respiratory tract infectionInfections and infestations———
Urinary tract infectionInfections and infestations———
PruritusSkin and subcutaneous tissue disorders———
Abdominal painGastrointestinal disorders———
PyrexiaGeneral disorders———
Platelet count decreasedInvestigations———
ArthralgiaMusculoskeletal and connective tissue disorders———
DyspnoeaRespiratory, thoracic and mediastinal disorders———
Dry eyeEye disorders———
Pain in extremityMusculoskeletal and connective tissue disorders———
Oropharyngeal painRespiratory, thoracic and mediastinal disorders———
Skin fissuresSkin and subcutaneous tissue disorders———
NeutropeniaBlood and lymphatic system disorders———
DyspepsiaGastrointestinal disorders———
Face oedemaGeneral disorders———
Non-cardiac chest painGeneral disorders———
Lower respiratory tract infectionInfections and infestations———
Alanine aminotransferase increasedInvestigations———
Blood creatinine increasedInvestigations———
Electrocardiogram QT prolongedInvestigations———
Neutrophil count decreasedInvestigations———
HyperkalaemiaMetabolism and nutrition disorders———
MyalgiaMusculoskeletal and connective tissue disorders———

Most-reported serious reactions: Influenza, Atrial fibrillation, Cardiac failure congestive, Ileus, Malaise, Hepatitis B, Pneumonia, Pulmonary sepsis.

Data from ClinicalTrials.gov NCT02197247 adverse events section.

Sponsor's own description

This is a Phase I, open-label, 2-part study in patients with a confirmed diagnosis of epidermal growth factor receptor (EGFR) mutation positive (EGFRm+) non-small cell lung cancer (NSCLC), who have progressed following prior therapy with an approved EGFR tyrosine kinase inhibitor (TKI) agent. Part A will assess the effect of rifampicin on the pharmacokinetic (PK) parameters of AZD9291 and metabolites AZ5104 and AZ7550 following multiple oral dosing of both rifampicin and AZD9291 in a fasted state. Part B will allow patients further access to AZD9291 after the PK phase (Part A) and will provide for additional safety data collection. All patients who complete Part A will be able to enter part B, and continue to receive AZD9291 80 mg once daily until: disease progression; they are no longer deriving clinical benefit; or any other reason.

Publications & conference data

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

  1. The effect of itraconazole and rifampicin on the pharmacokinetics of osimertinib.
    Vishwanathan K, Dickinson PA, So K, Thomas K, et al · · 2018 · cited 57× · PMID 29381826 · DOI 10.1111/bcp.13534
  2. Development, Verification, and Prediction of Osimertinib Drug-Drug Interactions Using PBPK Modeling Approach to Inform Drug Label.
    Pilla Reddy V, Walker M, Sharma P, Ballard P, et al · · 2018 · cited 48× · PMID 29468841 · DOI 10.1002/psp4.12289
  3. Erratum: Development, Verification, and Prediction of Osimertinib Drug-Drug Interactions Using PBPK Modeling Approach to Inform Drug Label.
    · 2019 · PMID 30901159 · DOI 10.1002/psp4.12386

Verify or expand the search:

Other trials of Pharmacokinetic sampling - AZD9291

Trials testing the same drug.

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Currently open trials in the same condition.

Other AstraZeneca trials

Trials by the same sponsor.

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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/NCT02197247.

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