Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Digestive System Diseases

Musculoskeletal Diseases

Rare Diseases

Melanoma

Gastrointestinal Stromal Tumors

Giant Cell Tumors

Giant Cell Tumor of Tendon Sheath

Pigmented Villonodular Synovitis

Adjuvants, Anesthesia

Central Nervous System Depressants

Psychotropic Drugs

All Drugs and Chemicals

Hypoglycemic Agents

Midazolam

Tolbutamide

Anesthetics

Hypnotics and Sedatives

Anti-Anxiety Agents

Anesthetics, Intravenous

Anesthetics, General

GABA Modulators

Neurotransmitter Agents

Part 1 (Drug-drug Interaction Phase):

On Day 1, all participants will receive a single oral dose each of midazolam (2 mg) and tolbutamide (500 mg). On Day 3, pexidartinib (800 mg/d) in twice daily (400 mg BID) dosing will be initiated and continue throughout the remainder of Part 1 and into Part 2. On the first day of pexidartinib treatment (Day 3), a single dose of midazolam (2 mg) and tolbutamide (500 mg) will be co-administered with the morning pexidartinib dose (400 mg). On Day 13, a single dose of midazolam (2 mg) and tolbutamide (500 mg) will be co-administered with the morning dose of pexidartinib (400 mg).

Part 2 (Efficacy and Safety Phase):

All participants will continue to receive pexidartinib 400 mg BID.

Pexidartinib is formulated as opaque, white, 200-mg capsules

Pexidartinib

Global Clinical Leader

This study has two parts.

Part 1 will evaluate how pexidartinib affects the way the body processes CYP3A4 and CYP2C9 substrates using midazolam and tolbutamide, respectively, as probe agents.

Part 2 will test the efficacy and safety of pexidartinib treatment in various tumor types.

In Part 2, the same participants will continue to receive pexidartinib twice daily.

Participants will be allowed to continue using pexidartinib as long as the participant derives benefit.

Open-label, single sequence study with 2 parts

Effect of Pexidartinib on the Way the Body Processes CYP3A4 and CYP2C9 Substrates (Pharmacokinetics)

An Open-label, Single Sequence, Crossover Drug-drug Interaction Study Assessing the Effect of Pexidartinib on the Pharmacokinetics of CYP3A4 and CYP2C9 Substrates in Patients

De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

Plasma samples for midazolam were collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24, and 48 hours (h) (±10 minutes up to 1 h, ±10% thereafter) on Days 1 to 3, and also when co-administered with pexidartinib on Days 3 (to 5) and Days 13 (to 15).

Plasma samples for tolbutamide were collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24, and 48 h (±10 min up to 1 h, ±10% thereafter) on Days 1 to 3, and also when co-administered with pexidartinib on Days 3 (to 5) and Days 13 (to 15).

Adverse events that emerge during treatment, having been absent pre-treatment, or worsens relative to the pre-treatment state.

Plasma samples for pexidartinib and its metabolite were collected at predose, 0.5, 1, 2, 2.5, 3, 4, 6, 8, and 10 (±1) h after the first dose on Day 3, and at steady state when co-administered with midazolam and tolbutamide on Day 13.

Plasma samples for midazolam and 1-hydroxy midazolam were to be collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 (±10 min up to 8 h), 10 (±2), 24 (±2), and 48 (±2) hours on Days 1 to 3 and also when co-administered with pexidartinib on Days 3 to 5 and Days 13 to 15.

Plasma samples for midazolam were collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24, and 48 hours (h) (±10 minutes up to 1 h, ±10% thereafter) on Days 1 to 3, and also when co-administered with pexidartinib on Days 3 (to 5) and Days 13 (to 15).

Plasma pharmacokinetic parameters calculated for Midazolam metabolite. 1-hydroxy midazolam and midazolam for the MPR value.

Daiichi Sankyo

A treatment emergent adverse event (TEAE) was defined as an adverse event that emerges during treatment of Pexidartinib, having been absent pretreatment (Pexidartinib), or worsens relative to the pre-treatment (Pexidartinib) state.

On Day 1, participants received the single oral dose of midazolam (2 mg) and tolbutamide (500 mg).

On Day 3, pexidartinib (800 mg/day) administered as 400 mg twice daily (BID) was initiated and continued throughout the remainder of Part 1 and into Part 2. On the first day of pexidartinib treatment (Day 3), a single dose of midazolam (2 mg) and tolbutamide (500 mg) was co-administered with the morning pexidartinib dose (400 mg).

On Day 13, a single dose of midazolam (2 mg) and tolbutamide (500 mg) was co-administered with the morning dose of pexidartinib (400 mg).

Part 1: Drug-drug Interaction Phase

All participants received pexidartinib twice daily (BID) dosing in 28-day cycles at the 400 mg/day dose for up to one year.

Part 2: Pexidartinib Only

All participants who received pexidartinib in Part 1 and Part 2 of the study.

All Participants

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Contact for Clinical Trial Information

All participants received a single oral dose of midazolam (2 mg) on Day 1.

Part 1: Midazolam Only

All participants received a single oral dose of midazolam (2 mg) on Day 3 concomitantly with pexidartinib and on Day 13 following approximately 10 days of pexidartinib twice daily (BID) dosing.

Part 1: Pexidartinib + Midazolam (Cycle 1, Day 1)

Part 1: Pexidartinib + Midazolam (Cycle 1, Day 11)

Pharmacokinetic parameters were assessed in the Pharmacokinetic Evaluable population.

Pharmacokinetic Analysis: Maximum Concentration (Cmax) for Midazolam

All participants received a single oral dose of tolbutamide (500 mg) on Day 1.

Part 1: Tolbutamide Only

All participants received a single oral dose of tolbutamide (500 mg) concomitantly with pexidartinib and on Days 3 and 13 following approximately 10 days of pexidartinib twice daily (BID) dosing.

Part 1: Pexidartinib + Tolbutamide (Cycle 1, Day 1)

Part 1: Pexidartinib + Tolbutamide (Cycle 1, Day 11)

Pharmacokinetic Analysis: Maximum Concentration (Cmax) for Tolbutamide

Pharmacokinetic Analysis: Time to Maximum Concentration (Tmax) for Midazolam

Pharmacokinetic Analysis: Time to Maximum Concentration (Tmax) for Tolbutamide

Pharmacokinetic Analysis: Area Under the Curve to the Last Observable Concentration (AUClast) for Midazolam

Pharmacokinetic Analysis: Area Under the Curve to the Last Observable Concentration (AUClast) for Tolbutamide

TEAEs

Pexidartinib-related TEAEs

Treatment-emergent serious adverse events (SAEs)

Pexidartinib-related SAEs

Treatment-emergent adverse events (TEAEs) were assessed in the Safety Analysis population.

Overall Summary of Treatment-emergent Adverse Events

ZAAD-1006a

Pexidartinib was administered orally as a total daily dose of 800 mg (400 mg BID) starting from Day 3.

Spots Global Cancer Trial Database for Effect of Pexidartinib on the Way the Body Processes CYP3A4 and CYP2C9 Substrates (Pharmacokinetics)

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial