Clinical trial NCT03864042: Pharmacokinetic Drug-drug Interaction Study of Encorafenib and Binimetinib on Probe Drugs in Patients With BRAF V600-mutant Melanoma or Other Advanced Solid Tumors
Official title: An Open-label Phase 1 Study to Evaluate Drug-Drug Interactions of Agents Co-Administered With Encorafenib and Binimetinib in Patients With BRAF V600-mutant Unresectable or Metastatic Melanoma or Other Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Metastatic Melanoma
Keywords: solid tumor
melanoma
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: Pierre Fabre Laboratories
First posted: 2019-03-06
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is an open-label, 3-arm, fixed-sequence study to evaluate the effect of single and multiple oral doses of encorafenib in combination with binimetinib on the single oral dose pharmacokinetics (PK) of cytochrome P450 (CYP) enzyme probe substrates using a probe cocktail, on an organic anion-transporting polypeptide/breast cancer resistance protein (OATP/BCRP) substrate using rosuvastatin and on a CYP2B6 substrate using bupropion. The effect of multiple oral doses of the moderate cytochrome P450 (CYP) inhibitor modafinil on encorafenib in combination with binimetinib will also be assessed. The study will have 2 treatment phases, a drug-drug interaction (DDI) phase followed by a post-DDI phase.


Eligibility criteria: Key Inclusion Criteria - Patients must meet all of the inclusion criteria to be eligible for enrollment into the study:

* Histologically confirmed diagnosis of locally advanced, unresectable or metastatic cutaneous melanoma or unknown primary melanoma American Joint Committee on Cancer (AJCC) Stage IIIB, IIIC or IV; or other BRAF V600-mutant advanced solid tumors
* Presence of BRAF V600E and/or V600K mutation in tumor tissue prior to enrollment, as determined using a local test;
* Evidence of measurable or non-measurable lesions
* Patient with unresectable locally advanced or metastatic melanoma who has received no prior treatment or progressed on or after prior systemic therapy; Note: Prior therapy with a BRAF proto-oncogene serine-threonine protein kinase (BRAF) inhibitor and/or a mitogen-activated protein (MAP) kinase (MEK) inhibitor is permitted except in the regimen immediately prior to study entry
* Patient with other (non-melanoma) BRAF V600E and/or V600K -mutant advanced solid tumors who has progressed on standard therapy or for whom there are no available standard therapies; Note: Prior therapy with a BRAF inhibitor and/or a MEK inhibitor is permitted except in the regimen immediately prior to study entry
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
* Adequate bone marrow, hepatic and renal function as specified in the protocol
* ARM 1 ONLY: Non-smoker who has not used nicotine containing products for at least 3 months prior to the first dose.

Key Exclusion Criteria - Patients meeting any of the following criteria are not eligible for enrollment in the study:

* Symptomatic brain metastasis. Patients previously treated or untreated for these conditions that are asymptomatic in the absence of corticosteroid and anti-epileptic therapy are allowed. Brain metastases must be stable, with imaging (e.g., magnetic resonance imaging \[MRI\] or computed tomography \[CT\] demonstrating no current evidence of progressive brain metastases at screening);
* Symptomatic or untreated leptomeningeal disease;
* History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes);
* Clinically significant cardiac disease
* Known hyper-coagulability risks other than malignancy (e.g., Factor V Leiden syndrome);
* Thromboembolic event except catheter-related venous thrombosis ≤ 12 weeks prior to starting study treatment.
* Discontinuation of prior BRAF and/or MEK inhibitor treatment due to left ventricular dysfunction, pneumonitis/interstitial lung disease, or retinal vein occlusion;
* ARM 1 ONLY: Positive urine cotinine test at screening
* ARM 3 ONLY:

  * History of psychosis, depression or mania;
  * History of angioedema;
  * History of mitral valve prolapse;
  * History of left ventricular hypertrophy;

Primary outcomes:
measure: Maximum Concentration (Cmax) of Plasma Midazolam on Day -7, Day 1, and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: Cmax of Plasma Total 1-OH Midazolam on Day -7, Day 1, and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: Cmax of Plasma Free 1-OH Midazolam on Day -7, Day 1, and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: Cmax of Plasma Glucuronide Conjugated 1-Hydroxymidazolam on Day -7, Day 1, and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: Cmax of Plasma Absolute Caffeine on Day -7, Day 1, and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: Cmax of Plasma Baseline-Adjusted Caffeine on Day -7, Day 1, and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: Cmax of Plasma Paraxanthine on Day -7, Day 1, and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: Cmax of Plasma Omeprazole on Day -7, Day 1, and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: Cmax of Plasma 5-OH Omeprazole on Day -7, Day 1, and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: Cmax of Plasma Rosuvastatin on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: Cmax of Plasma Bupropion on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: Cmax of Plasma Hydroxybupropion on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: Area Under the Concentration-Time Profile From Time 0 to The Time of The Last Quantifiable Concentration (AUClast) of Plasma Midazolam on Day -7, Day 1, and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: AUClast of Plasma Total 1-OH Midazolam on Day -7, Day 1, and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: AUClast of Plasma Free 1-OH Midazolam on Day -7, Day 1, and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: AUClast of Plasma Glucuronide Conjugated 1-Hydroxymidazolam on Day -7, Day 1, and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: AUClast of Plasma Absolute Caffeine on Day -7, Day 1, and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: AUClast of Plasma Baseline-Adjusted Caffeine on Day -7, Day 1, and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: AUClast of Plasma Paraxanthine on Day -7, Day 1, and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: AUClast of Plasma Omeprazole on Day -7, Day 1, and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: AUClast of Plasma 5-OH Omeprazole in Arm 1 on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: AUClast of Plasma Rosuvastatin on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: AUClast of Plasma Bupropion on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: AUClast of Plasma Hydroxybupropion on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: The Amount Eliminated Via Urine Over an 8-Hour Period (Ae0-8) of Losartan on Day -7, Day 1 and Day 14
timeFrame: 0 to 8 hours after dosing on Days -7, 1 and 14
measure: Ae0-8 of E-3174 on Day -7, Day 1 and Day 14
timeFrame: 0 to 8 hours after dosing on Days -7, 1 and 14
measure: Ae0-8 of Dextromethorphan on Day -7, Day 1 and Day 14
timeFrame: 0 to 8 hours after dosing on Days -7, 1 and 14
measure: Ae0-8 of Dextrorphan on Day -7, Day 1 and Day 14
timeFrame: 0 to 8 hours after dosing on Days -7, 1 and 14
measure: Cmax of Plasma Encorafenib on Day 14 and Day 21 in Arm 3
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21
measure: Cmax of Plasma LHY746 on Day 14 and Day 21 in Arm 3
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21
measure: AUClast of Plasma Encorafenib on Day 14 and Day 21 in Arm 3
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21
measure: AUClast of Plasma LHY746 on Day 14 and Day 21 in Arm 3
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21
Secondary outcomes:
measure: Ratio of AUClast Values of the Metabolite Compared to Parent (MRAUClast) for 1-OH Midazolam/Midazolam on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: Ratio of AUC From Time Zero Extrapolated to Infinity (AUCinf) Values of the Metabolite Compared to Parent (MRAUCinf) for 1-OH Midazolam/Midazolam on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: MRAUClast for Paraxanthine/Caffeine on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: MRAUClast for 5-OH Omeprazole/Omeprazole on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: MRAUCinf for 5-OH Omeprazole/Omeprazole on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: MRAUClast for Hydroxybupropion/Bupropion on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: MRAUClast for LHY746/Encorafenib in Arm 3 on Day 14 and Day 21
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21
measure: Ratio of Cmax Values of the Metabolite Compared to Parent (MRCmax) for 1-OH Midazolam/Midazolam on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: MRCmax for Paraxanthine/Caffeine on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: MRCmax for 5-OH Omeprazole/Omeprazole on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: MRCmax for Hydroxybupropion/Bupropion on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: MRCmax for LHY746/Encorafenib in Arm 3 on Day 14 and Day 21
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21
measure: Ratio of Ae0-8 Values of the Metabolite Compared to Parent (MRAe0-8) for E-3174/Losartan on Day -7, Day 1 and Day 14
timeFrame: 0 to 8 hours after dosing on Days -7, 1 and 14
measure: MRAe0-8 for Dextrorphan/Dextromethorphan on Day -7, Day 1 and Day 14
timeFrame: 0 to 8 hours after dosing on Days -7, 1 and 14
measure: Time to Reach Cmax (Tmax) of Plasma Midazolam on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: Tmax of Plasma Total 1-OH Midazolam on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14.
measure: Tmax of Plasma Free 1-OH Midazolam on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: Tmax of Plasma Glucuronide Conjugated 1-Hydroxymidazolam on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: Tmax of Plasma Absolute Caffeine on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: Tmax of Plasma Baseline-Adjusted Caffeine on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: Tmax of Plasma Paraxanthine on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: Tmax of Plasma Omeprazole on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours (+/- 15 minutes window for each time-point) postdose on Day 1 and Day 14
measure: Tmax of Plasma 5-OH Omeprazole on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours (+/- 15 minutes window for each time-point) postdose on Day 1 and Day 14
measure: Tmax of Plasma Rosuvastatin on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: Tmax of Plasma Bupropion on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: Tmax of Plasma Hydroxybupropion on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: AUCinf of Plasma Midazolam on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: AUCinf of Plasma Total 1-OH Midazolam on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: AUCinf of Plasma Free 1-OH Midazolam on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: AUCinf of Plasma Glucuronide Conjugated 1-Hydroxymidazolam on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: AUCinf of Plasma Omeprazole on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: AUCinf of Plasma 5-OH Omeprazole on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: AUCinf of Plasma Rosuvastatin on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: AUCinf of Plasma Bupropion on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: Percent of AUC Extrapolated (AUC%Extrap) of Plasma Midazolam on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: AUC%Extrap of Plasma Total 1-OH Midazolam on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: AUC%Extrap of Plasma Free 1-OH Midazolam on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: AUC%Extrap of Plasma Glucuronide Conjugated 1-Hydroxymidazolam on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: AUC%Extrap of Plasma Absolute Caffeine on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: AUC%Extrap of Plasma Baseline-Adjusted Caffeine on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: AUC%Extrap of Plasma Omeprazole on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: AUC%Extrap of Plasma 5-OH Omeprazole on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: Apparent Terminal Elimination Rate Constant (Kel) of Plasma Midazolam on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: Kel of Plasma Total 1-OH Midazolam on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: Kel of Plasma Free 1-OH Midazolam on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: Kel of Plasma Glucuronide Conjugated 1-Hydroxymidazolam on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: Kel of Plasma Absolute Caffeine on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: Kel of Plasma Baseline-Adjusted Caffeine on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: Kel of Plasma Omeprazole on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: Kel of Plasma 5-OH Omeprazole on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: Terminal Elimination Half-Life (T1/2) of Plasma Midazolam on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14.
measure: T1/2 of Plasma Total 1-OH Midazolam on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: T1/2 of Plasma Free 1-OH Midazolam on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: T1/2 of Plasma Glucuronide Conjugated 1-Hydroxymidazolam on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14.
measure: T1/2 of Plasma Absolute Caffeine on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: T1/2 of Plasma Baseline-Adjusted Caffeine on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: T1/2 of Plasma Omeprazole on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: T1/2 of Plasma 5-OH Omeprazole on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: T1/2 of Plasma Rosuvastatin on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: T1/2 of Plasma Bupropion on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: Apparent Clearance (CL/F) of Plasma Midazolam on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: CL/F of Plasma Omeprazole on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: Apparent Total Volume of Distribution Following Oral Administration (Vz/F) of Plasma Midazolam on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: Vz/F of Plasma Omeprazole on Day -7, Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
measure: Percentage of Dose Recovered in Urine (Fe) for Losartan on Day -7, Day 1 and Day 14
timeFrame: Predose, and 0 to 8 hours postdose on Day -7, Day 1 and Day 14
measure: Fe for E-3174 on Day -7, Day 1 and Day 14
timeFrame: 0 to 8 hours postdose on Day -7, Day 1 and Day 14
measure: Fe for Dextromethorphan on Day -7, Day 1 and Day 14
timeFrame: 0 to 8 hours postdose on Day -7, Day 1 and Day 14
measure: Fe for Dextrorphan on Day -7, Day 1 and Day 14
timeFrame: 0 to 8 hours postdose on Day -7, Day 1 and Day 14
measure: Cmax of Encorafenib on Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14.
measure: Cmax of LHY746 on Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14
measure: Cmax of Binimetinib on Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14.
measure: Cmax of AR00426032 on Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14
measure: AUClast of Encorafenib on Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14.
measure: AUClast of LHY746 on Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14
measure: AUClast of Binimetinib on Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14
measure: AUClast of AR00426032 on Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14
measure: Tmax of Encorafenib on Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14.
measure: Tmax of LHY746 on Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours (+/- 15 minutes window for each time-point) postdose on Day 1 and Day 14
measure: Tmax of Binimetinib on Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14.
measure: Tmax of AR00426032 on Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14
measure: AUCinf of Encorafenib on Day 1
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1
measure: AUCinf of Binimetinib on Day 1
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1.
measure: AUCinf of AR00426032 on Day 1
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1
measure: T1/2 of Encorafenib on Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14
measure: T1/2 of LHY746 on Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14
measure: T1/2 of Binimetinib on Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14
measure: T1/2 of AR00426032 on Day 1 and Day 14
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1 and Day 14
measure: AUC%Extrap of Encorafenib on Day 1
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1
measure: AUC%Extrap of LHY746 on Day 1
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1
measure: AUC%Extrap of Binimetinib on Day 1
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1
measure: AUC%Extrap of AR00426032 on Day 1
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1
measure: Kel of Encorafenib on Day 1
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1
measure: Kel of LHY746 on Day 1
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1
measure: Kel of Binimetinib on Day 1
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1
measure: Kel of AR00426032 on Day 1
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1
measure: CL/F of Encorafenib on Day 1
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1.
measure: CL/F of Binimetinib on Day 1
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1.
measure: Vz/F of Encorafenib on Day 1
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1.
measure: Vz/F of Binimetinib on Day 1
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 1.
measure: Cmax of Binimetinib on Day 14 and Day 21
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21
measure: Cmax of AR00426032 on Day 14 and Day 21
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21
measure: AUClast of Binimetinib on Day 14 and Day 21
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21
measure: AUClast of AR00426032 on Day 14 and Day 21
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21
measure: Tmax of Encorafenib on Day 14 and Day 21
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21
measure: Tmax of LHY746 on Day 14 and Day 21
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21
measure: Tmax of Binimetinib on Day 14 and Day 21
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21
measure: Tmax of AR00426032 on Day 14 and Day 21
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21
measure: T1/2 of Encorafenib on Day 14 and Day 21
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21
measure: T1/2 of LHY746 on Day 14 and Day 21
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21
measure: T1/2 of Binimetinib on Day 14 and Day 21
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21
measure: T1/2 of AR00426032 on Day 14 and Day 21
timeFrame: Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the DDI Phase
timeFrame: After 1st dose of encorafenib/binimetinib on Day 1 and up to Day 28 visit in the DDI Phase
measure: Number of Participants With Laboratory Abnormalities in the DDI Phase
timeFrame: After 1st dose of encorafenib/binimetinib on Day 1 and up to Day 28 visit in the DDI Phase
measure: Number of Participants With Notable Abnormalities in Vital Signs in the DDI Phase
timeFrame: After 1st dose of encorafenib/binimetinib on Day 1 and up to Day 28 visit in the DDI Phase
measure: Number of Participants With Notable Electrocardiogram (ECG) Findings in the DDI Phase
timeFrame: After 1st dose of encorafenib/binimetinib on Day 1 and up to Day 28 visit in the DDI Phase
measure: Number of Participants With Left Ventricular Ejection Fraction (LVEF) Abnormalities in the DDI Phase
timeFrame: After 1st dose of encorafenib/binimetinib on Day 1 and up to Day 28 visit in the DDI Phase
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Post-DDI Phase
timeFrame: After 1st dose of encorafenib/binimetinib on Day 1 up to 30 days after the post-DDI Phase
Other outcomes:
Locations:
city: Orange
country: United States
facility: UC Irvine Health
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital - Anschutz Cancer Pavilion (ACP)
state: Colorado
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Hopkins
country: United States
facility: Hopkins Eye Clinic
state: Minnesota
city: Maple Grove
country: United States
facility: Park Nicollet Eye Clinic
state: Minnesota
city: Saint Paul
country: United States
facility: Regions Cancer Care Center
state: Minnesota
city: Saint Paul
country: United States
facility: HealthPartners Specialty Center-Eye Care
state: Minnesota
city: Canton
country: United States
facility: Gabrail Cancer Center Research
state: Ohio
city: Knoxville
country: United States
facility: University of TN Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Mary Crowley Cancer Research - Medical City Hospital
state: Texas
city: West Valley City
country: United States
facility: Utah Cancer Specialists
state: Utah
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Montreal
country: Canada
facility: Sir Mortimer B Davis Jewish General Hospital
state: Quebec
city: Montreal
country: Canada
facility: McGill University Health Center
state: Quebec
city: Montrea
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Amsterdam
country: Netherlands
facility: Het Nederlands Kanker Instituut Antoni Van Leeuwenhoek Ziekenhuis
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
city: Barcelona
country: Spain
facility: Hospital del Mar
city: El Palmar
country: Spain
facility: Hospital Clinico Universitario Virgen de la Arrixaca
city: Lleida
country: Spain
facility: Hospital Universitari Arnau de Vilanova
city: Madrid
country: Spain
facility: Hospital Beata Maria Ana
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Clinica Rementeria
city: Madrid
country: Spain
facility: MD Anderson Cancer Center Madrid
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro - CIOCC
city: Sevilla
country: Spain
facility: CERCO
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: