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Drug cocktail

Phase 1

Malignant Melanoma | Small molecule | Oncology |Roche Holding AG|Last Updated: Aug 15, 2017

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Trial Design

UNCONTROLLED
Total Trials1
Total Enrollment25

FDA Designations

No designations recorded

Clinical trial landscape

Drug cocktail · 1 trial · 1 indication

Phase 1 1
NCT01001299A Pharmacokinetic Study of RO5185426 in Combination With a Drug Cocktail in Patients With Metastatic MelanomaMalignant Melanoma
COMPLETED25 Analytics
PHASE1COMPLETED
A Pharmacokinetic Study of RO5185426 in Combination With a Drug Cocktail in Patients With Metastatic Melanoma
Malignant MelanomaUnlock trial analytics

Study Endpoints

Primary Endpoints

Geometric Mean Ratio of Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Observed Sampling Time (AUC[0-last]) of Probe Parent Drugs
Day 1, 20: 0, 1, 3, 4, 6, 8, 24 hours, additionally for caffeine 0.5, 1.5, 2, 12, 18, 48, 72, 96, 120,dextromethorphan 0.5, 1.5, 2, 12, 18, 48,midazolam 0.08, 0.25, 0.5, 0.75, 2, 10,omeprazole 0.5, 1.5, 2, 2.5, 12, 18,S-warfarin 12, 48, 72, 96, 120 hours

AUC(0-last) was defined as the area under the plasma concentration-time curve calculated using the linear trapezoidal rule from time zero to the last observed sampling time. To assess the potential for drug-drug interactions, the geometric mean ratios and corresponding 90 percent (%) confidence interval (CI) of AUC(0-last) of parent probe drug before (Day 1) and after treatment with vemurafenib (Day 20) was calculated. Ratio and corresponding 90% CI of AUC(0-last) (Day 20/Day 1) for each of the 5 probe drugs is reported.

Geometric Mean Ratio of Maximum Plasma Concentration (Cmax) of Probe Parent Drugs
Day 1, 20: 0, 1, 3, 4, 6, 8, 24 hours, additionally for caffeine 0.5, 1.5, 2, 12, 18, 48, 72, 96, 120,dextromethorphan 0.5, 1.5, 2, 12, 18, 48,midazolam 0.08, 0.25, 0.5, 0.75, 2, 10,omeprazole 0.5, 1.5, 2, 2.5, 12, 18,S-warfarin 12, 48, 72, 96, 120 hours

To assess the potential for drug-drug interactions, the geometric mean ratios and corresponding 90% CI of Cmax of parent probe drug before (Day 1) and after treatment with vemurafenib (Day 20) was calculated. Ratio and corresponding 90% CI of Cmax (Day 20/Day 1) for each of the 5 probe drugs is reported.

Geometric Mean Ratio of AUC(0-last) and Cmax of Metabolites of Probe Parent Drugs
Day 1, 20: 0, 1, 3, 4, 6, 8, 24 hours, additionally for paraxanthine 0.5, 1.5, 2, 12, 18, 48, 72, 96, 120, dextrorphan 0.5, 1.5, 2, 12, 18, 48, OH-midazolam 0.08, 0.25, 0.5, 0.75, 2, 10, OH-omeprazole 0.5, 1.5, 2, 2.5, 12, 18 hours

AUC(0-last) was defined as the area under the plasma concentration-time curve calculated using the linear trapezoidal rule from time zero to the last observed sampling time. To assess the potential for drug-drug interactions, the geometric mean ratios and corresponding 90% CI of AUC(0-last) and Cmax of metabolites of parent probe drug before (Day 1) and after treatment with vemurafenib (Day 20) was calculated. Ratio and corresponding 90% CI of AUC(0-last) and Cmax (Day 20/Day 1) for each of the 4 probe drug metabolites is reported (paraxanthine \[caffeine metabolite\], dextrorphan \[dextromethorphan metabolite\], OH-midazolam \[midazolam metabolite\], OH-omeprazole (omeprazole metabolite); S-warfarin does not have a metabolite).

AUC(0-last) and Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC[0-inf]) of Probe Parent Drugs and Their Metabolites on Day 1
Day 1: 0, 1, 3, 4, 6, 8, 24 hours, additionally for caffeine 0.5, 1.5, 2, 12, 18, 48, 72, 96, 120,dextromethorphan 0.5, 1.5, 2, 12, 18, 48,midazolam 0.08, 0.25, 0.5, 0.75, 2, 10,omeprazole 0.5, 1.5, 2, 2.5, 12, 18,S-warfarin 12, 48, 72, 96, 120 hours

AUC(0-last) was defined as the area under the plasma concentration-time curve calculated using the linear trapezoidal rule from time zero to the last observed sampling time. AUC(0-inf) was defined as the area under the plasma concentration-time curve calculated using the linear trapezoidal rule from time zero extrapolated to infinity. Timeframe reported for parent probe drug is also applicable for their metabolite except S-warfarin, as S-warfarin does not have a metabolite.

AUC(0-last) and AUC(0-inf) of Probe Parent Drugs and Their Metabolites on Day 20
Day 20: 0, 1, 3, 4, 6, 8, 24 hours, additionally for caffeine 0.5, 1.5, 2, 12, 18, 48, 72, 96, 120,dextromethorphan 0.5, 1.5, 2, 12, 18, 48,midazolam 0.08, 0.25, 0.5, 0.75, 2, 10,omeprazole 0.5, 1.5, 2, 2.5, 12, 18,S-warfarin 12, 48, 72, 96, 120 hours

AUC(0-last) was defined as the area under the plasma concentration-time curve calculated using the linear trapezoidal rule from time zero to the last observed sampling time. AUC(0-inf) was defined as the area under the plasma concentration-time curve calculated using the linear trapezoidal rule from time zero extrapolated to infinity. Timeframe reported for parent probe drug is also applicable for their metabolite except S-warfarin, as S-warfarin does not have a metabolite.

Area Under the Plasma Concentration-Time Curve From Time Zero to 8, 12, and 24 Hours (AUC[0-8], AUC[0-12], AUC[0-24]) of Vemurafenib
0, 0.5, 1, 2, 4, 8, 12, 13, 14, 16, 18, 24 hours on Day 19

Area under the plasma concentration-time curve calculated using the linear trapezoidal rule from time zero to 8, 12, and 24 hours (AUC\[0-8\], AUC\[0-12\], AUC\[0-24\], respectively).

Cmax of Probe Parent Drugs and Their Metabolites on Day 1
Day 1: 0, 1, 3, 4, 6, 8, 24 hours, additionally for caffeine 0.5, 1.5, 2, 12, 18, 48, 72, 96, 120,dextromethorphan 0.5, 1.5, 2, 12, 18, 48,midazolam 0.08, 0.25, 0.5, 0.75, 2, 10,omeprazole 0.5, 1.5, 2, 2.5, 12, 18,S-warfarin 12, 48, 72, 96, 120 hours

Timeframe reported for parent probe drug is also applicable for their metabolite except S-warfarin as S-warfarin does not have a metabolite.

Cmax of Probe Parent Drugs and Their Metabolites on Day 20
Day 20: 0, 1, 3, 4, 6, 8, 24 hours, additionally for caffeine 0.5, 1.5, 2, 12, 18, 48, 72, 96, 120,dextromethorphan 0.5, 1.5, 2, 12, 18, 48,midazolam 0.08, 0.25, 0.5, 0.75, 2, 10,omeprazole 0.5, 1.5, 2, 2.5, 12, 18,S-warfarin 12, 48, 72, 96, 120 hours

Timeframe reported for parent probe drug is also applicable for their metabolite except S-warfarin as S-warfarin does not have a metabolite.

Cmax of Vemurafenib
0, 0.5, 1, 2, 4, 8, 12, 13, 14, 16, 18, 24 hours on Day 19
Time to Reach Maximum Plasma Concentration (Tmax) of Probe Parent Drugs and Their Metabolites on Day 1
Day 1: 0, 1, 3, 4, 6, 8, 24 hours, additionally for caffeine 0.5, 1.5, 2, 12, 18, 48, 72, 96, 120,dextromethorphan 0.5, 1.5, 2, 12, 18, 48,midazolam 0.08, 0.25, 0.5, 0.75, 2, 10,omeprazole 0.5, 1.5, 2, 2.5, 12, 18,S-warfarin 12, 48, 72, 96, 120 hours

Timeframe reported for parent probe drug is also applicable for their metabolite except S-warfarin as S-warfarin does not have a metabolite.

Tmax of Probe Parent Drugs and Their Metabolites on Day 20
Day 20: 0, 1, 3, 4, 6, 8, 24 hours, additionally for caffeine 0.5, 1.5, 2, 12, 18, 48, 72, 96, 120,dextromethorphan 0.5, 1.5, 2, 12, 18, 48,midazolam 0.08, 0.25, 0.5, 0.75, 2, 10,omeprazole 0.5, 1.5, 2, 2.5, 12, 18,S-warfarin 12, 48, 72, 96, 120 hours

Timeframe reported for parent probe drug is also applicable for their metabolite except S-warfarin as S-warfarin does not have a metabolite.

Tmax of Vemurafenib
0, 0.5, 1, 2, 4, 8, 12, 13, 14, 16, 18, 24 hours on Day 19
Trough Plasma Concentration (Cmin) of Vemurafenib
Before morning dose (0 hour) on Day 19
Apparent Elimination Half-Life in Plasma (t1/2) of Probe Parent Drugs and Their Metabolites on Day 1
Day 1: 0, 1, 3, 4, 6, 8, 24 hours, additionally for caffeine 0.5, 1.5, 2, 12, 18, 48, 72, 96, 120,dextromethorphan 0.5, 1.5, 2, 12, 18, 48,midazolam 0.08, 0.25, 0.5, 0.75, 2, 10,omeprazole 0.5, 1.5, 2, 2.5, 12, 18,S-warfarin 12, 48, 72, 96, 120 hours

Timeframe reported for parent probe drug is also applicable for their metabolite except S-warfarin as S-warfarin does not have a metabolite.

t1/2 of Probe Parent Drugs and Their Metabolites on Day 20
Day 20: 0, 1, 3, 4, 6, 8, 24 hours, additionally for caffeine 0.5, 1.5, 2, 12, 18, 48, 72, 96, 120,dextromethorphan 0.5, 1.5, 2, 12, 18, 48,midazolam 0.08, 0.25, 0.5, 0.75, 2, 10,omeprazole 0.5, 1.5, 2, 2.5, 12, 18,S-warfarin 12, 48, 72, 96, 120 hours

Timeframe reported for parent probe drug is also applicable for their metabolite except S-warfarin as S-warfarin does not have a metabolite.

Apparent Plasma Clearance (CL/F) of Probe Parent Drugs on Day 1
Day 1: 0, 1, 3, 4, 6, 8, 24 hours, additionally for caffeine 0.5, 1.5, 2, 12, 18, 48, 72, 96, 120,dextromethorphan 0.5, 1.5, 2, 12, 18, 48,midazolam 0.08, 0.25, 0.5, 0.75, 2, 10,omeprazole 0.5, 1.5, 2, 2.5, 12, 18,S-warfarin 12, 48, 72, 96, 120 hours

Drug clearance was a quantitative measure of the rate at which a drug substance was removed from the body. Clearance obtained after oral dose was influenced by the fraction of the dose absorbed.

CL/F of Probe Parent Drugs on Day 20
Day 20: 0, 1, 3, 4, 6, 8, 24 hours, additionally for caffeine 0.5, 1.5, 2, 12, 18, 48, 72, 96, 120,dextromethorphan 0.5, 1.5, 2, 12, 18, 48,midazolam 0.08, 0.25, 0.5, 0.75, 2, 10,omeprazole 0.5, 1.5, 2, 2.5, 12, 18,S-warfarin 12, 48, 72, 96, 120 hours

Drug clearance was a quantitative measure of the rate at which a drug substance was removed from the body. Clearance obtained after oral dose was influenced by the fraction of the dose absorbed.

Secondary Endpoints

Percentage of Participants With a Confirmed Best Overall Response of Complete Response (CR) or Partial Response (PR)
Screening up to approximately 3.5 years (assessed at Screening, Day 1 of Cycle 3 thereafter Day 1 of every other cycle [every 2 months] and at end of study)
Duration of Response
Screening up to approximately 3.5 years (assessed at Screening, Day 1 of Cycle 3 thereafter Day 1 of every other cycle [every 2 months] and at end of study)
Time to Response
Screening up to approximately 3.5 years (assessed at Screening, Day 1 of cycle 3 thereafter Day 1 of every other cycle [every 2 months] and at end of study)
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Study Design & Arms

MaskingNONE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Single armEXPERIMENTAL -

Interventions

NameTypeDescription
Drug cocktailDRUGDrug cocktail (caffeine, warfarin + vitamin K, omeprazole, dextromethorphan, midazolam) orally once daily, day 1 and day 20
RO5185426DRUG960 mg orally twice daily
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites5

Inclusion Criteria: * Adult patient \>/= 18 years of age * Malignant melanoma (Stage IV, AJCC) * Patients who are treatment-naive or have received prior systemic treatments for metastatic melanoma. Time elapsed between previous treatment for metastatic disease and first administration of study drug...

Countries:United States
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Frequently asked questions about Drug cocktail

What is Drug cocktail used for in Malignant Melanoma?

Drug cocktail is an investigational small molecule being studied for the treatment of malignant melanoma. It is currently in Phase 1 clinical development, meaning it has not yet been approved by regulatory authorities. The drug is being evaluated for its safety and pharmacokinetic profile in patients with metastatic melanoma.

Who makes Drug cocktail?

Drug cocktail is being developed by Roche Holding AG, a biopharmaceutical company traded under the ticker RHHBY. The company is conducting clinical research to evaluate the drug's potential in oncology, specifically for malignant melanoma. Roche is responsible for the drug's development program and clinical trial oversight.

What phase is Drug cocktail in?

Drug cocktail is in Phase 1 clinical development. This is the earliest stage of human testing, focused on evaluating the drug's safety, tolerability, and pharmacokinetics. The drug is investigational and has not received regulatory approval for any use. Its development is ongoing, with one completed Phase 1 trial to date.

What clinical trials is Drug cocktail in?

Drug cocktail has one completed clinical trial, identified as NCT01001299. This was a Phase 1 pharmacokinetic study of RO5185426 in combination with a drug cocktail in patients with metastatic melanoma. The trial enrolled 25 participants in the United States and was not randomized or blinded.

Is Drug cocktail the same as RO5185426?

Drug cocktail is a combination therapy that includes RO5185426 as one of its components. The clinical trial NCT01001299 evaluated the pharmacokinetics of RO5185426 when administered alongside a drug cocktail. This combination approach was studied in patients with metastatic melanoma to understand how the drugs interact.