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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Nova Laboratories Limited
ClinicalTrials.gov Identifier:
NCT01697020
First received: September 20, 2012
Last updated: November 28, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Acute Lymphoblastic Leukemia
Drug: Mercaptopurine 20mg/ml oral suspension
Drug: Mercaptopurine 50mg tablet
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A SINGLE CENTER, SINGLE-DOSE, OPEN-LABEL, RANDOMIZED, TWO-PERIOD CROSSOVER STUDY TO ASSESS THE BIOEQUIVALENCE OF AN ORAL MERCAPTOPURINE SUSPENSION 100 mg / 5 mL VERSUS AN ORAL MERCAPTOPURINE TABLET 50 mg (PURINETHOL®) IN AT LEAST 62 HEALTHY MALE SUBJECTS UNDER FASTING CONDITIONS

Resource links provided by NLM:


Further study details as provided by Nova Laboratories Limited:

Primary Outcome Measures:
  • Bioequivalence [ Time Frame: Within 7 days ] [ Designated as safety issue: No ]

    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-∞)).


Enrollment: 70
Study Start Date: September 2012
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
Mercaptopurine 20mg/ml Oral Suspension
Drug: Mercaptopurine 20mg/ml oral suspension
50mg
Other Name: Xaluprine
Active Comparator: Arm 2
Mercaptopurine 50mg tablets
Drug: Mercaptopurine 50mg tablet
50mg
Other Name: Purinethol

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • Subjects who plan to procreate within 12 weeks after IMP administration, or not willing to practice reliable forms of contraception during the study and for at least 12 weeks after the last dose of IMP.
  • Immunization using a live organism vaccine within 4 weeks prior to the first dosing of IMP.
  • Any specific IMP safety concern.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01697020

Locations
South Africa
Parexel International, Bloemfontein Early Phase Clinical Unit
Bloemfontein, South Africa
Sponsors and Collaborators
Nova Laboratories Limited
  More Information

No publications provided

Responsible Party: Nova Laboratories Limited
ClinicalTrials.gov Identifier: NCT01697020     History of Changes
Other Study ID Numbers: INV298
Study First Received: September 20, 2012
Last Updated: November 28, 2013
Health Authority: South Africa: Medicines Control Council

Additional relevant MeSH terms:
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Leukemia
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
6-Mercaptopurine
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014