Rare Diseases

All Conditions

Oculocerebral Syndrome With Hypopigmentation

Micronutrients

All Drugs and Chemicals

Vasodilator Agents

Lipid Regulating Agents

Hematinics

Vitamins

Niacinamide

Niacin

Nicotinic Acids

Folic Acid

Vitamin B Complex

Trace Elements

Nicotinamide

Nicotinic Acid

Vitamin B3

Folate

Vitamin B9

Pimasertib capsule administration at a single dose of 60 milligram (mg) orally on Day 1 in Part A.

Pimasertib Capsule (Part A)

Pimasertib tablet administration at a single dose of 60 mg orally on Day 3 in Part A.

Pimasertib Tablet (Part A)

Pimasertib tablet administration at a single dose of 60 mg orally on Day 1 in Part A.

Pimasertib capsule administration at a single dose of 60 mg orally on Day 3 in Part A.

Subjects completing Part A to receive pimasertib capsule at a dose of 60 mg orally twice daily in cycles of 21 days each in Part B and trial extension phase until disease progression, intolerable toxicity, subject withdrawal, loss to follow-up or death.

Pimasertib Capsule (Part B and trial extension phase)

Medical Responsible

This is a Phase 1, multi-center, open-label, single-dose, 2 period, 2 sequence cross-over trial to investigate the relative bioavailability of 2 solid oral pimasertib formulations in cancer subjects (Part A), followed by open-label pimasertib administration (Part B and trial extension phase).

Relative Bioavailability of Pimasertib in Cancer Patients

A Multi-Center, Open-Label, Single 60 mg Dose, Two Period, Two Sequence Cross-Over Trial to Investigate the Relative Bioavailability of Two Solid Oral Pimasertib Formulations in Cancer Patients

Maximum observed plasma concentration (Cmax) was calculated for Part A Pimasertib 60 mg Capsule and tablet.

Area under the plasma concentration-time curve from time zero to the last sampling time (AUC0-t) at which the concentration was at or above the lower limit of quantification.

Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.

An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug administration until 30 days after the last dose of study drug administration that were absent before treatment or that worsened relative to pre treatment state.

CR as per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 defined as disappearance of all target lesions except lymph nodes (LN); LN must have a decrease in the short axis to less than (\<)10 millimeter (mm).

PR as per RECIST v1.1 defined as 30% decrease in sum of diameters of target lesions taking as reference the baseline sum diameters.

SD as per RECIST v1.1 defined as neither shrinkage to qualify for PR nor increase to qualify for progressive disease (PD) taking the smallest sum diameters on study as reference. PR = 30% decrease in sum of diameters of target lesions taking as reference the baseline sum diameters; PD = 20% increase in sum of diameters of target lesions; the appearance of \>=1 new lesions.

PD as per RECIST v1.1 defined as 20% increase in sum of diameters of target lesions; the appearance of \>=1 new lesions.

EMD Serono

A single dose of 2 Pimasertib 30 mg capsule administered orally in one of the intervention periods in part A of the study.

Part A: Pimasertib 60 mg Capsule

A single dose of 3 Pimasertib 20 mg tablet administered orally in one of the intervention periods in part A of the study.

Part A: Pimasertib 60 mg Tablet

Pimasertib 2 capsule 30 mg orally twice daily up to 4 cycles of 21 days each in Part B and trial extension phase until disease progression, intolerable toxicity, subject withdrawal, loss to follow-up or death.

Part B: Pimasertib Capsule (BID)

It included all the subjects randomized to receive either Pimasertib 60 mg capsule and Pimasertib 60 mg tablet first in Part A and Pimasertib 60 mg capsule in Part B of the study.

Entire Study Population

Age, Continuous

Sex: Female, Male

Safety analysis set included all subjects who received at least one dose of investigational medicinal product (IMP).

Merck KGaA Communication Center

Pharmacokinetic (PK) analysis set included all subjects who received the Part A IMP, had compliance with IMP intake in Part A, at least one post-treatment PK sample from each treatment period and absence of protocol deviations affecting bioavailability.

Maximum Observed Plasma Concentration (Cmax)

A single dose of 2 Pimasertib 30 mg capsule administered orally in one of the intervention periods in part A of the study

PK analysis set included all subjects who received the Part A IMP, had compliance with IMP intake in Part A, at least one post-treatment PK sample from each treatment period and absence of protocol deviations affecting bioavailability. Here N (number of participants analysed) signifies the number of subjects analysed for this outcome measure.

Area Under the Plasma Concentration-time Curve From Zero to Infinity (AUC0-inf)

PK analysis set included all subjects who received the Part A IMP, had compliance with IMP intake in Part A, at least one post-treatment PK sample from each treatment period and absence of protocol deviations affecting bioavailability.

Time to Reach Maximum Observed Plasma Concentration (Tmax)

PK analysis set included all subjects who received the Part A IMP, had compliance with IMP intake in Part A, at least one post-treatment PK sample from each treatment period and absence of protocol deviations affecting bioavailability. Here N (number of participants analyzed) signifies the number of subjects analysed for this outcome measure.

Apparent Terminal Half-life (t1/2)

Apparent Total Body Clearance (CL/f)

Apparent Volume of Distribution (Vz/f)

Terminal Rate Constant (λz)

Area Under the Plasma Concentration-time Curve From Zero to the Last Quantifiable Concentration (AUC 0-t)

TEAEs

Serious TEAEs

TEAEs leading to discontinuation

Part B: Pimasertib Capsule

Safety analysis set included all subjects who received at least one dose of IMP.

Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation

Part B: Number of Subjects Who Experienced Complete Response (CR)

Part B: Number of Subjects Who Experienced Partial Response (PR)

Part B: Number of Subjects Who Experienced Stable Disease (SD)

Part B: Number of Subjects Who Experienced Progressive Disease (PD)

A single dose of 2 Pimasertib 30 mg capsule administered orally on Day 1 in first intervention period followed by a single dose of 3 Pimasertib 20 mg tablet single dose administered orally on Day 3, of Part A of the study. A washout period of 48 hours was maintained between the administration of the two treatments.

Part A: Pimasertib Capsule Then Pimasertib Tablet

A single dose of 3 Pimasertib 20 mg tablet administered orally on Day 1 in first intervention period followed by a single dose of 2 Pimasertib 30 mg capsule single dose administered orally on Day 3, of Part A of the study. A washout period of 48 hours was maintained between the administration of the two treatments.

Spots Global Cancer Trial Database for Relative Bioavailability of Pimasertib in Cancer Patients

Trial Identification

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Interventions

Study Description

Keywords

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