Bioequivalence Study Between Temozolomide Oral Suspension (Ped-TMZ) and Temodal® Capsules

Primary objective:

• Evaluate bioequivalence between Temozolomide Oral Suspension and Temodal® capsules for oral administration.

Secondary objectives:

• Define the pharmacokinetic parameters of Temozolomide Oral Suspension.
• Assess the buccal safety of Temozolomide Oral Suspension.

Study Overview

• Status: Completed
• Conditions: Therapeutic Equivalency
• Intervention / Treatment: Drug: Ped-TMZ

Detailed Description

The study is an open label, randomized, crossover, 2-period study in 30 male/female patients with primary CNS malignancies. Patients will receive, under fasting conditions, 200 mg/m² of Temozolomide Oral Suspension (Ped-TMZ) or Temodal®, as single oral administration in 2 different study periods depending on the randomization, with no wash out period between administrations.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Bordeaux, France, 33075
    • Chu de Bordeaux
  • Marseille, France, 13005
    • Hopital De La Timone (ap-hm)
  • Rhône
    • Bron, Rhône, France, 69500
      • Service de neuro-oncologie - Hospices Civils de Lyon

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with newly diagnosed glioblastoma multiforme treated with temozolomide (200mg/m2) as monotherapy and patients with recurrent or progressive malignant glioma treated with temozolomide as monotherapy (200mg/m2).
• Male and female patients at least 18 of age.
• Non-pregnant, non-breast feeding female.
• Body mass index (weight/height²) in the range of 18.5 to 30 kg/m².
• Having given a written informed consent

Exclusion Criteria:

• Co-administration of sodium valproate
• Patients with (naso)gastric tubes
• Patients receiving 150 mg/m² and not eligible to the 200 mg/m² dose

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Ped-TMZ; Single oral administration on D1 or D2 according to randomization at the dose of 200 mg/m2. Ped-TMZ will be administered using the provided dosing oral syringes and followed by a glass of 240 ml of water (for mouth rinsing) in sitting position and under fasting condition.	Drug: Ped-TMZ; Ped-TMZ will be administered using the provided dosing oral syringes and followed by a glass of 240 ml of water (for mouth rinsing) in sitting position and under fasting condition for at least 8 hours before dosing; Other Names: Temozolomide Oral Suspension
ACTIVE_COMPARATOR: Temodal capsule; Single oral administration on D1 or D2 according to randomization at the dose of 200 mg/m2. The administration will take place around 8:00 a.m. followed with 240 mL of tap water, in sitting position and under fasting condition	Drug: Ped-TMZ; Ped-TMZ will be administered using the provided dosing oral syringes and followed by a glass of 240 ml of water (for mouth rinsing) in sitting position and under fasting condition for at least 8 hours before dosing; Other Names: Temozolomide Oral Suspension

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary pharmacokinetic parameter: Cmax	The Cmax pharmacokinetic parameter will be determined from temozolomide plasma concentrations	Day 1 or Day 2
Primary pharmacokinetic parameter: AUC0-t	The AUC0-t pharmacokinetic parameter will be determined from temozolomide plasma concentrations	Day 1 or Day 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary pharmacokinetic parameter: AUC0-inf	The AUC0-inf pharmacokinetic parameter will be determined from temozolomide plasma concentrations	Day 1 or Day 2
Secondary pharmacokinetic parameter: tmax	The tmax pharmacokinetic parameter will be determined from temozolomide plasma concentrations	Day 1 and Day 2
Secondary pharmacokinetic parameter: λ	The λ pharmacokinetic parameter will be determined from temozolomide plasma concentrations	Day 1 and Day 2
Secondary pharmacokinetic parameter: t1/2	The t1/2 pharmacokinetic parameters will be determined from temozolomide plasma concentrations	Day 1 and Day 2
Secondary pharmacokinetic parameter: residual area	The residual area of temozolomide will be determined from temozolomide plasma concentrations	Day 1 and Day 2

Collaborators and Investigators

• Sponsor: Orphelia Pharma
• Investigators: Study Director: Caroline Lemarchand, PharmD, Orphelia Pharma

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 25, 2020
• Primary Completion (ACTUAL): December 17, 2021
• Study Completion (ACTUAL): December 17, 2021

Study Registration Dates

• First Submitted: March 27, 2020
• First Submitted That Met QC Criteria: July 8, 2020
• First Posted (ACTUAL): July 13, 2020

Study Record Updates

• Last Update Posted (ACTUAL): February 23, 2022
• Last Update Submitted That Met QC Criteria: February 21, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Temozolomide
• Other Study ID Numbers: ORP-TMZ-I-a

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No