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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Therapeutic Equivalency

Intervention / Treatment
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* Drug: Ped-TMZ


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ped-TMZ<br>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<br>* 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<br>* Other names: Temozolomide Oral Suspension;|
| Active Comparator: Temodal capsule<br>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<br>* 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<br>* Other names: Temozolomide Oral Suspension;|

What is the study measuring?
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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 |