Bioequivalence of An Oral Mercaptopurine Suspension 100 Mg / 5 Ml Versus Tablet in Healthy Male Subjects Under Fasting Conditions

NCT01697020 | Completed Phase 1

• 1 other identifier: INV298
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to determine whether the test product, mercaptopurine oral 100 mg/5 mL suspension, and the reference product, Purinethol® 50 mg tablets are bioequivalent. For this purpose the PK profile of 6-mercaptopurine (6-MP) will be compared after administration of a single dose of each of the two formulations, under fasting conditions. The secondary objective is to assess the safety and tolerability of the test product, mercaptopurine oral 100 mg/5 mL suspension.

Conditions

Acute Lymphoblastic Leukemia

Outcome Measures

Primary Outcomes (1)

• Bioequivalence

  At each treatment period, pharmacokinetic blood samples will be collected through the indwelling venous cannula at the following times: pre-dose and post-dose at 0.17, 0.33, 0.5, 0.75, 1.0, 1.33, 1.67, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10.0 and 12.0 hours. The primary outcome measures will be * Maximum observed plasma concentration (Cmax). * AUC time zero to time of the last quantifiable concentration (AUC(0-t)) * Area under the plasma concentration versus time data pairs, with extrapolation to infinity (AUC(0-∞)).

  Within 7 days

Study Arms (2)

Arm 1

EXPERIMENTAL

Mercaptopurine 20mg/ml Oral Suspension

Drug: Mercaptopurine 20mg/ml oral suspension

Arm 2

ACTIVE COMPARATOR

Mercaptopurine 50mg tablets

Drug: Mercaptopurine 50mg tablet

Interventions

Mercaptopurine 20mg/ml oral suspension DRUG

50mg

Also known as: Xaluprine

Arm 1

Mercaptopurine 50mg tablet DRUG

50mg

Also known as: Purinethol

Arm 2

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male subjects, 18 years to 50 years inclusive at time of last administration of the IMP.
• Body Mass Index (BMI) between 18.5 and 30 kg/m2.
• Body mass not less than 50 kg.
• Medical history, physical examination, standard 12-lead electrocardiogram (ECG) and laboratory investigations: Findings clinically acceptable or within laboratory reference ranges for the relevant laboratory tests, unless the investigator considers the deviation to be irrelevant for the purpose of the study.
• Non-smokers.

You may not qualify if:

• Current alcohol use \> 21 units of alcohol per week for males.
• Regular exposure to substances of abuse (other than alcohol) within the past year.
• Use of any medication, prescribed or over-the-counter or herbal remedies, within 2 weeks prior to the first administration of IMP except if this will not affect the outcome of the study in the opinion of the investigator.
• Participation in another study with an experimental drug, where the last administration of the previous IMP was within 8 weeks before the first administration of IMP in this study.
• Treatment within the previous 3 months before the first administration of IMP with any drug with a well-defined potential for adversely affecting a major organ or system.
• A major illness during the 3 months before commencement of the screening period.
• Subjects with a deficient, low or intermediate TPMT enzyme activity by means of phenotyping.
• Subjects who participated in previous azathioprine/mercaptopurine studies within six months will be excluded.
• Relevant history or laboratory or clinical findings indicative of acute or chronic disease, likely to influence study outcome.
• Donation or loss of blood equal to or exceeding 500 mL during the 8 weeks before the first administration of IMP.
• Diagnosis of hypotension or hypertension made during the screening period or current diagnosis of hypertension.
• Resting pulse of \> 100 beats per minute or \< 45 beats per minute during the screening period, either supine or standing.
• Positive testing for HIV and/or Hepatitis B and/or Hepatitis C.
• Positive urine screen for drugs of abuse.
• Positive urine screen for tobacco use.

Sponsors & Collaborators

• Nova Laboratories Limited: lead

Study Sites (1)

Parexel International, Bloemfontein Early Phase Clinical Unit

Bloemfontein, South Africa

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Mercaptopurine; Suspensions; Tablets

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Sulfhydryl Compounds; Sulfur Compounds; Organic Chemicals; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Colloids; Complex Mixtures; Dosage Forms; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2012
• First Posted: October 2, 2012
• Study Start: September 1, 2012
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: December 2, 2013

Record last verified: 2013-11

Locations

ZA (1)