Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Central Nervous System Stimulants

All Drugs and Chemicals

Anti-Arrhythmia Agents

Antihypertensive Agents

Adjuvants, Anesthesia

Central Nervous System Depressants

Psychotropic Drugs

Lipid Regulating Agents

Gastrointestinal Agents

Analgesics

Antitussive Agents

Respiratory System Agents

Bone Density Conservation Agents

Vasoconstrictor Agents

Cardiotonic Agents

Anti-Obesity Agents

Other Dietary Supplements

Caffeine

Losartan

Midazolam

Rosuvastatin Calcium

Modafinil

Omeprazole

Levomethorphan

Dextromethorphan

Bupropion

Calcium

Calcium, Dietary

Anesthetics

Hypnotics and Sedatives

Anti-Anxiety Agents

Anesthetics, Intravenous

Anesthetics, General

GABA Modulators

Neurotransmitter Agents

Anticholesteremic Agents

Hypolipidemic Agents

Antimetabolites

Hydroxymethylglutaryl-CoA Reductase Inhibitors

Enzyme Inhibitors

Phosphodiesterase Inhibitors

Angiotensin II

Giapreza

Angiotensinogen

Angiotensin II Type 1 Receptor Blockers

Angiotensin Receptor Antagonists

Antacids

Anti-Ulcer Agents

Proton Pump Inhibitors

Antidepressive Agents

Dopamine

Dopamine Uptake Inhibitors

Dopamine Agents

Cytochrome P-450 Enzyme Inhibitors

Phenylpropanolamine

Guaifenesin

Chlorpheniramine, phenylpropanolamine drug combination

Excitatory Amino Acid Antagonists

Analgesics, Opioid

Narcotics

Patients will receive a single oral dose of the CYP Probe Cocktail on Day -7, Day 1, and Day 14:

* 25 mg losartan oral tablet
* 30 mg dextromethorphan oral capsule
* 50 mg caffeine oral liquid
* 20 mg omeprazole oral capsule
* 2 mg midazolam oral syrup

encorafenib/binimetinib continuous daily dosing starting Day 1:

* 450 mg (6 x 75 mg) encorafenib oral capsules once daily (QD)
* 45 mg (3 x 15 mg) binimetinib oral tablet twice daily (BID)

All drugs will be taken within 10 minutes.

Patients will receive a single oral dose of rosuvastatin and bupropion once on Day -7, Day 1 and Day 14:

* 10 mg rosuvastatin oral tablet
* 75 mg bupropion immediate release (IR) oral tablet

encorafenib/binimetinib continuous daily dosing starting Day 1:

* 450 mg (6 x 75 mg) encorafenib oral capsules once daily (QD)
* 45 mg (3 x 15 mg) binimetinib oral tablet twice daily (BID)

All drugs will be taken within 10 minutes.

Patients will begin encorafenib/binimetinib continuous daily dosing starting Day 1:

* 450 mg (6 x 75 mg) encorafenib oral capsules once daily (QD)
* 45 mg (3 x 15 mg) binimetinib oral tablet twice daily (BID)

then receive continuous treatment of modafinil on Day 15 through Day 21:

- 400 mg modafinil tablet once daily (QD)

losartan

dextromethorphan

caffeine

omeprazole

midazolam

rosuvastatin

bupropion immediate release (IR)

encorafenib

binimetinib

modafinil

Pfizer CT.gov Call Center

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.

Pharmacokinetic Drug-drug Interaction Study of Encorafenib and Binimetinib on Probe Drugs in Patients With BRAF V600-mutant Melanoma or Other Advanced Solid Tumors

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

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Pierre Fabre Laboratories

Pfizer

Anti-Infective Agents

Itraconazole

Digoxin

Rifampin

Hydroxyitraconazole

Clotrimazole

Miconazole

Antifungal Agents

Hormones

Hormone Antagonists

Cytochrome P-450 CYP3A Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Antitubercular Agents

Protective Agents

Enrolled subjects were treated with JMKX001899 on Day 1. Itraconazole was administered orally once daily after a standardized meal from Day 4 to Day 6. JMKX001899 and itraconazole were administered simultaneously after a standardized meal on Day 7. On Day 8 to Day 9, itraconazole was orally administered once after a standard meal

Enrolled subjects were treated with JMKX001899 after high fat meal on Day 1 and an empty stomach on Day 4. Rifampin was administered orally once daily on an empty stomac from Day 7 to Day 15, Day 17and Day 18. JMKX001899 and Rigampin were administered simultaneously on an empty stomach on Day 16.

Enrolled subjects were treated with Cocktail substrate (Midazolam, dextromethorphan, Rosuvastatin and digoxin) on an empty stomach on Day 1. JMKX001899 was administered orally once daily after a standardized meal from Day 9 to Day 20 and Day 22. Cocktail and JMKX001899 were administered simultaneously on an empty stomach on Day 8 and Day 21.

JMKX001899

Rosuvastatin

digoxin

JING XU

This is an open-label, non-randomized, clinical study to evaluate the drug interaction between itraconazole, rifampin or Cocktail and JMKX001899 in healthy subjects. A total of three cohorts of 72 healthy subjects were planned to be enrolled in each cohort.

Study to Evaluate the Drug-drug Interaction of JMKX001899 in Healthy Subjects

a Single-center, Non-randomized, Open-label, Self-controlled Phase 1 Clinical Study to Evaluate Drug-drug Interactions of JMKX001899 Tablets in Healthy Subjects

Jemincare

Amino Acids

Dacomitinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Tyrosine

PF-00299804: Patients take oral 45 mg PF-00299804 once daily starting on Cycle 1 Day 1 until disease progression or unacceptable toxicities occur. One cycle equals 21 days. Dextromethorphan: Patient take a single 30 mg oral dose of dextromethorphan HBr three days prior to Cycle 1 Day 1, and then on Cycle 2 Day 7.

PF-00299804

Research in test tubes suggests that may affect cytochrome P450 2D6 (CYP2D6), an important enzyme that is responsible for eliminating many drugs that cancer patients need to take, including dextromethorphan. The purpose of this study is to test the impact of PF-00299804 on the activity of CYP2D6, and how the human body handles dextromethorphan.

To assess the effect of repeated dosing with 45 mg QD PF-00299804 on the pharmacokinetics of dextromethorphan, a CYP2D6 probe, in cancer patients with advanced malignant solid tumors.

A Study To Test The Impact Of PF- 00299804 On How The Body Handles Dextromethorphan In Cancer Patients

A Phase 1 Open Label, Single Arm Trial To Evaluate The Effect Of Pf-00299804 On The Pharmacokinetics Of Dextromethorphan In Patients With Advanced Malignant Solid Tumors

Dextrorphan is an active metabolite of dextromethorphan.

Area under the plasma concentration time-curve from time zero (pre-dose) to the last measured concentration (AUClast). Dextrorphan is an active metabolite of dextromethorphan.

AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0-t) plus AUC (t-inf). Dextrorphan is an active metabolite of dextromethorphan.

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. Dextrorphan is an active metabolite of dextromethorphan.

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population PK modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

The UMR was calculated as the ratio of the amount of dextrmotherphan excreted in urine from time zero to 8 hours post-dose on Day -3 to the amount of dextrorphan excreted in urine from time zero to 8 hours post-dose on Day -3.

The UMR was calculated as the ratio of the amount of dextrmotherphan excreted in urine from time zero to 8 hours post-dose on Day 7 to the amount of dextrorphan excreted in urine from time zero to 8 hours post-dose on Day 7.

BOR: investigator assessment by Response Evaluation Criteria in Solid Tumors (RECIST), recorded from treatment start until disease progression/recurrence. Complete Response: disappearance of all lesions. Partial Response (PR): \>=30% decrease in sum of longest diameters (SLDs) of target lesions (TLs) taking as reference baseline SLD. Progressive disease (PD): \>=20% increase in SLD of TLs taking as reference smallest SLD since treatment start, or appearance of \>=1 new lesion. Stable disease: neither shrinkage for PR nor increase for PD taking as reference smallest SLD since treatment start.

Time in weeks from the first documentation of objective tumor response to objective tumor progression or death due to any cancer. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 7. DR was calculated for the subgroup of participants with a confirmed objective tumor response.

Time in months from start of study treatment to first documentation of objective tumor progression or death due to cancer, whichever comes first. TTP was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 30.437. Tumor progression was determined from oncologic assessment data (where data meet the criteria for PD).

Roswell Park Cancer Institute

South Texas Accelerated Research Therapeutics (START)

The same event may appear as both an adverse event (AE) and a serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.

PF-00299804 45 milligram (mg) tablet orally once daily, starting from Cycle 1 Day 1, continuously for 21-day cycles until disease progression or unacceptable toxicities along with single dose of dextromethorphan hydrobromide 30 mg orally 3 days prior to Cycle 1 Day 1 (Day -3) and on Day 7 of Cycle 2.

PF-00299804 45 mg + Dextromethorphan 30 mg

Age, Continuous

Sex: Female, Male

Dextromethorphan AUCinf and t1/2 results not reported as data did not support calculation since levels of dextromethorphan were not tracked long enough for reliable estimation.

Pfizer ClinicalTrials.gov Call Center

Dextrorphan

Pharmacokinetic (PK) analysis population included all participants that were extensive metabolizers and treated, had at least 1 of PK parameters of primary interest in at least 1 treatment period. Here, N (number of participants analyzed) signifies who received PF-00299804 daily without interruptions or dose reductions prior to Day 7 of Cycle 2.

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Dextromethorphan and Dextrorphan 3 Days Prior to PF-00299804 Dosing

PK analysis population included all participants that were extensive metabolizers and treated, had at least 1 of PK parameters of primary interest in at least 1 treatment period. Here, N (number of participants analyzed) signifies who received PF-00299804 daily without interruptions or dose reductions prior to Day 7 of Cycle 2.

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Dextromethorphan and Dextrorphan on Cycle 2 Day 7

Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) For Dextrorphan 3 Days Prior to PF-00299804 Dosing

Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) For Dextrorphan on Cycle 2 Day 7

Maximum Observed Plasma Concentration (Cmax) For Dextromethorphan and Dextrorphan 3 Days Prior to PF-00299804 Dosing

Maximum Observed Plasma Concentration (Cmax) For Dextromethorphan and Dextrorphan on Cycle 2 Day 7

Time to Reach Maximum Observed Plasma Concentration (Tmax) For Dextromethorphan and Dextrorphan 3 Days Prior to PF-00299804 Dosing

Time to Reach Maximum Observed Plasma Concentration (Tmax) For Dextromethorphan and Dextrorphan on Cycle 2 Day 7

Plasma Decay Half-Life (t1/2) For Dextrorphan 3 Days Prior to PF-00299804 Dosing

Plasma Decay Half-Life (t1/2) For Dextrorphan on Cycle 2 Day 7

Results not reported as data did not support calculation since levels of dextromethorphan were not tracked long enough for reliable estimation.

Oral Clearance For Dextromethorphan 3 Days Prior to PF-00299804 Dosing

Oral Clearance For Dextromethorphan on Cycle 2 Day 7

PK parameter analysis population: all participants enrolled who were extensive metabolizers (EM), \& treated who had at least 1 PK parameter of primary interest in at least 1 treatment period. EMs were defined as participants with a baseline UMR ≤0.3 \& were either ultrarapid, extensive, or intermediate metabolizers as predicted by CYP2D6 genotyping.

Urinary Metabolic Ratio (UMR) of Dextromethorphan to Dextrorphan 3 Days Prior to PF-00299804 Dosing

Urinary Metabolic Ratio (UMR) of Dextromethorphan to Dextrorphan on Cycle 2 Day 7

Complete response

Partial response

Stable/No response

Objective progression

Response anslysis set: all enrolled participants who received at least 1 dose of study medication and had an adequate baseline tumor assessment.

Best Overall Response (BOR)

Participants with a response (CR or PR) in response analysis set.

Duration of Response (DR)

Time to Tumor Progression (TTP)

Ratio of AUC was a derived parameter. As the primary endpoint for the study was not met, only the primary parameter AUC was analyzed and reported. Other parameters were not derived for this study based on investigator's decision.

Ratio of Dextromethorphan Area Under the Curve to Dextrorphan Area Under the Curve 3 Days Prior to PF-00299804 Dosing

Ratio of Dextromethorphan Area Under the Curve to Dextrorphan Area Under the Curve on Cycle 2 Day 7

Overall Study

Blood and Lymph Conditions

Immune System Diseases

Lymphoma

Hodgkin Disease

Lymphoma, Non-Hodgkin

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Hodgkin Lymphoma

Acute Graft Versus Host Disease

Sub-therapeutic probe drug administration to measure phenoconversion.

Rachel Conyers, MBBS (Hons)

Marliese Alexander, Doctor of Philosophy

PEGASUS aims to test acceptability and feasibility of studying phenoconversion (the change in metabolism phenotype) using probe medications in a paediatric oncology patient population. The study will be conducted in patients (6-25 years of age) with Hodgkin lymphoma or non-Hodgkin lymphoma as exemplar cohort, but with the understanding that cancer-directed and supportive care medicines of the CYP3A4, CYP2C19, and CYP2D6 metabolic pathways are commonly utilised for the treatment of many paediatric, adolescent, young adult, and adult cancers.

The study involves administration of the probe medication at timepoints which align with pre-determined hospital visits for the treatment of lymphoma and subsequent blood draws to measure the metabolism of the probe medications.

The acceptability and feasibility of this study will inform future studies in phenoconversion within the paediatric cancer population to direct more personalised precision medicine.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pharmacokinetic Drug-drug Interaction Study of Encorafenib and Binimetinib on Probe Drugs in Patients With BRAF V600-mutant Melanoma or Other Advanced Solid Tumors	NCT03864042	Advanced Solid ... Metastatic Mela...	losartan dextromethorpha... caffeine omeprazole midazolam rosuvastatin bupropion immed... encorafenib binimetinib modafinil	18 Years -	Pfizer
Study to Evaluate the Drug-drug Interaction of JMKX001899 in Healthy Subjects	NCT06348290	Solid Tumor, Ad...	JMKX001899 Itraconazole Midazolam Rifampin dextromethorpha... Rosuvastatin digoxin	18 Years - 45 Years	Jemincare
Study to Evaluate the Drug-drug Interaction of JMKX001899 in Healthy Subjects	NCT06348290	Solid Tumor, Ad...	JMKX001899 Itraconazole Midazolam Rifampin dextromethorpha... Rosuvastatin digoxin	18 Years - 45 Years	Jemincare
A Study To Test The Impact Of PF- 00299804 On How The Body Handles Dextromethorphan In Cancer Patients	NCT00728468	Advanced Malign...	PF-00299804	18 Years -	Pfizer
A Study Investigating the Change in Metabolism Phenotype in Paediatric, Adolescent & Young Adults With Hodgkin or Non-Hodgkin Lymphoma.	NCT06383338	Hodgkin Lymphom... Non Hodgkin Lym...	Omeprazole Dextromethorpha...	6 Years - 25 Years	Murdoch Childrens Research Institute
A Study Investigating the Change in Metabolism Phenotype in Paediatric, Adolescent & Young Adults With Hodgkin or Non-Hodgkin Lymphoma.	NCT06383338	Hodgkin Lymphom... Non Hodgkin Lym...	Omeprazole Dextromethorpha...	6 Years - 25 Years	Murdoch Childrens Research Institute
Pharmacokinetic, Safety, and Efficacy Effects of Oral LBH589 on Dextromethorphan in Patients With Advanced or Metastatic Non-Small Cell Lung Cancer or Malignant Pleural Mesothelioma	NCT00535951	Carcinoma, Non-... Mesothelioma	LBH589	18 Years -	Novartis
PK Study to Assess Drug-drug Interaction and QTc Between Sitravatinib and a Cocktail of Substrates	NCT04887194	Advanced Solid ...	Sitravatinib Warfarin Dextromethorpha... Midazolam Digoxin Rosuvastatin Nivolumab	18 Years -	Mirati Therapeutics Inc.
A Study to Evaluate How Daily Dosing With Enzalutamide Affects the Metabolism of Caffeine and Dextromethorphan in Men With Prostate Cancer	NCT02225093	Pharmacokinetic... Pharmacokinetic... Prostate Cancer	Caffeine Dextromethorpha... Enzalutamide Enzalutamide Pl...	18 Years -	Astellas Pharma Inc
Study of Cobimetinib in Participants With Solid Tumors	NCT00467779	Solid Tumor	cobimetinib dextromethorpha... midazolam	18 Years -	Genentech, Inc.

Spots Global Cancer Trial Database for dextromethorphan