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bupropion immediate release

Phase 1

Advanced Solid Tumors | Small molecule | Oncology |Pfizer, Inc.|Last Updated: Sep 27, 2024

Target and mechanism

ModalitySmall molecule

Also known as bupropion immediate release (IR)

Success Probability

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Market & Valuation

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Trial Design

CONTROLLED
Total Trials1
Total Enrollment56

FDA Designations

No designations recorded

Clinical trial landscape

bupropion immediate release · 1 trial · 2 indications

Phase 1 1
NCT03864042Pharmacokinetic Drug-drug Interaction Study of Encorafenib and Binimetinib on Probe Drugs in Patients With BRAF V600-mutant Melanoma or Other Advanced Solid TumorsAdvanced Solid Tumors
COMPLETED56 Analytics
PHASE1COMPLETED
Pharmacokinetic Drug-drug Interaction Study of Encorafenib and Binimetinib on Probe Drugs in Patients With BRAF V600-mutant Melanoma or Other Advanced Solid Tumors
Advanced Solid TumorsUnlock trial analytics

Study Endpoints

Primary Endpoints

Maximum Concentration (Cmax) of Plasma Midazolam on Day -7, Day 1, and Day 14
Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14

Cmax is the maximum plasma concentration which was observed directly from the concentration-time data.

Cmax of Plasma Total 1-OH Midazolam on Day -7, Day 1, and Day 14
Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14

Cmax is the maximum plasma concentration which was observed directly from the concentration-time data. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.

Cmax of Plasma Free 1-OH Midazolam on Day -7, Day 1, and Day 14
Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14

Cmax is the maximum plasma concentration which was observed directly from the concentration-time data. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.

Cmax of Plasma Glucuronide Conjugated 1-Hydroxymidazolam on Day -7, Day 1, and Day 14
Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14

Cmax is the maximum plasma concentration which was observed directly from the concentration-time data. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.

Cmax of Plasma Absolute Caffeine on Day -7, Day 1, and Day 14
Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14

Cmax is the maximum plasma concentration which was observed directly from the concentration-time data. Due to dietary caffeine intake may resulted in positive pre-dose concentrations, absolute and/or baseline-adjusted caffeine were analyzed. Baseline adjusted concentration = measured concentration - \[predose concentration\*e\^(-Kel\*t)\], where Kel is terminal elimination rate constant based on actual measured concentration values for each profile and t is the actual sampling time.

Cmax of Plasma Baseline-Adjusted Caffeine on Day -7, Day 1, and Day 14
Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14

Cmax is the maximum plasma concentration which was observed directly from the concentration-time data. Due to dietary caffeine intake may resulted in positive pre-dose concentrations, absolute and/or baseline-adjusted caffeine were analyzed. Baseline adjusted concentration = measured concentration - \[predose concentration\*e\^(-Kel\*t)\], where Kel is terminal elimination rate constant based on actual measured concentration values for each profile and t is the actual sampling time.

Cmax of Plasma Paraxanthine on Day -7, Day 1, and Day 14
Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14

Cmax is the maximum plasma concentration which was observed directly from the concentration-time data. Paraxanthine was the metabolite of caffeine.

Cmax of Plasma Omeprazole on Day -7, Day 1, and Day 14
Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14

Cmax is the maximum plasma concentration which was observed directly from the concentration-time data.

Cmax of Plasma 5-OH Omeprazole on Day -7, Day 1, and Day 14
Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14

Cmax is the maximum plasma concentration which was observed directly from the concentration-time data. 5-OH Omeprazole was the metabolite of omeprazole.

Cmax of Plasma Rosuvastatin on Day -7, Day 1 and Day 14
Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14

Cmax is the maximum plasma concentration which was observed directly from the concentration-time data.

Cmax of Plasma Bupropion on Day -7, Day 1 and Day 14
Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14

Cmax is the maximum plasma concentration which was observed directly from the concentration-time data.

Cmax of Plasma Hydroxybupropion on Day -7, Day 1 and Day 14
Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14

Cmax is the maximum plasma concentration which was observed directly from the concentration-time data. Hydroxybupropion was the metabolite of bupropion.

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
Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14

AUClast is area under the concentration-time profile (AUC) from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method.

AUClast of Plasma Total 1-OH Midazolam on Day -7, Day 1, and Day 14
Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14

AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.

AUClast of Plasma Free 1-OH Midazolam on Day -7, Day 1, and Day 14
Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14

AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.

AUClast of Plasma Glucuronide Conjugated 1-Hydroxymidazolam on Day -7, Day 1, and Day 14
Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14

AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method. The metabolites of midazolam included total 1-OH midazolam, free 1-OH midazolam, and glucuronide conjugated 1-hydroxymidazolam.

AUClast of Plasma Absolute Caffeine on Day -7, Day 1, and Day 14
Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14

AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method. Due to dietary caffeine intake may resulted in positive pre-dose concentrations, absolute and/or baseline-adjusted caffeine were analyzed. Baseline adjusted concentration = measured concentration - \[predose concentration\*e\^(-Kel\*t)\], where Kel is terminal elimination rate constant based on actual measured concentration values for each profile and t is the actual sampling time.

AUClast of Plasma Baseline-Adjusted Caffeine on Day -7, Day 1, and Day 14
Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14

AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method. Due to dietary caffeine intake may resulted in positive pre-dose concentrations, absolute and/or baseline-adjusted caffeine were analyzed. Baseline adjusted concentration = measured concentration - \[predose concentration\*e\^(-Kel\*t)\], where Kel is terminal elimination rate constant based on actual measured concentration values for each profile and t is the actual sampling time.

AUClast of Plasma Paraxanthine on Day -7, Day 1, and Day 14
Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14

AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method. Paraxanthine was the metabolite of caffeine.

AUClast of Plasma Omeprazole on Day -7, Day 1, and Day 14
Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14

AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method.

AUClast of Plasma 5-OH Omeprazole in Arm 1 on Day -7, Day 1 and Day 14
Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14

AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method. 5-OH Omeprazole was the metabolite of omeprazole.

AUClast of Plasma Rosuvastatin on Day -7, Day 1 and Day 14
Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14

AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method.

AUClast of Plasma Bupropion on Day -7, Day 1 and Day 14
Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14

AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method.

AUClast of Plasma Hydroxybupropion on Day -7, Day 1 and Day 14
Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14

AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method. Hydroxybupropion was the metabolite of bupropion.

The Amount Eliminated Via Urine Over an 8-Hour Period (Ae0-8) of Losartan on Day -7, Day 1 and Day 14
0 to 8 hours after dosing on Days -7, 1 and 14

Ae0-8 is the amount excreted into the urine over the collection interval of 0 to 8 hours.

Ae0-8 of E-3174 on Day -7, Day 1 and Day 14
0 to 8 hours after dosing on Days -7, 1 and 14

Ae0-8 is the amount excreted into the urine over the collection interval of 0 to 8 hours. E-3174 was the metabolite of losartan.

Ae0-8 of Dextromethorphan on Day -7, Day 1 and Day 14
0 to 8 hours after dosing on Days -7, 1 and 14

Ae0-8 is the amount excreted into the urine over the collection interval of 0 to 8 hours.

Ae0-8 of Dextrorphan on Day -7, Day 1 and Day 14
0 to 8 hours after dosing on Days -7, 1 and 14

Ae0-8 is the amount excreted into the urine over the collection interval of 0 to 8 hours. Dextrorphan was the metabolite of dextromethorphan.

Cmax of Plasma Encorafenib on Day 14 and Day 21 in Arm 3
Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21

Cmax is the maximum plasma concentration which was observed directly from the concentration-time data.

Cmax of Plasma LHY746 on Day 14 and Day 21 in Arm 3
Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21

Cmax is the maximum plasma concentration which was observed directly from the concentration-time data. LHY746 was the metabolite of encorafenib.

AUClast of Plasma Encorafenib on Day 14 and Day 21 in Arm 3
Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21

AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method.

AUClast of Plasma LHY746 on Day 14 and Day 21 in Arm 3
Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day 14 and Day 21

AUClast is AUC from time 0 to the time of the last quantifiable concentration. It was calculated using the linear trapezoidal/linear interpolation method. LHY746 was the metabolite of encorafenib.

Secondary Endpoints

Ratio of AUClast Values of the Metabolite Compared to Parent (MRAUClast) for 1-OH Midazolam/Midazolam on Day -7, Day 1 and Day 14
Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
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
Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
MRAUClast for Paraxanthine/Caffeine on Day -7, Day 1 and Day 14
Predose, and 1, 2, 3, 4, 6 and 8 hours postdose on Day -7, Day 1 and Day 14
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Study Design & Arms

AllocationNON_RANDOMIZED
MaskingNONE
ModelSEQUENTIAL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Arm 1 - CYP Probe CocktailEXPERIMENTALPatients 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.
Arm 2 - Rosuvastatin and BupropionEXPERIMENTALPatients 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.
Arm 3 - ModafinilEXPERIMENTALPatients 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)

Interventions

NameTypeDescription
losartanDRUGtaken orally
dextromethorphanDRUGtaken orally
caffeineDRUGtaken orally
omeprazoleDRUGtaken orally
midazolamDRUGtaken orally
rosuvastatinDRUGtaken orally
bupropion immediate release (IR)DRUGtaken orally
encorafenibDRUGtaken orally
binimetinibDRUGtaken orally
modafinilDRUGtaken orally
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites29

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...

Countries:United StatesBelgiumCanadaNetherlandsSpain
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Competitive Landscape -Other Solid Tumors 9 trials (matched to "Advanced Solid Tumors")