Bioequivalence Study for an Isotretinoin

Bioequivalence Study for an Isotretinoin Pharmaceutical Preparation - Capsules. Crossover, Randomized, Single Dose, Two Treatments, Two Periods and Two Sequences With Meal (Breakfast) Study

The objective of this study was to confirm if two formulations of isotretionin (capsules) are bioequivalent.

Test product was Oratane® 20 mg (Laboratorios Dermatológicos Darier) and reference product Roaccutan® 20 mg (Productos Roche). Two capsules administered together were the single dosage.

The study was prospective, open-label, randomized, crossover, single dose, with 02 treatments, 02 sequences and 02 periods, under fed conditions.

The population was composed of 36 healthy volunteers, male adults between 18-45 years.

The comparative bioavailability of the two formulations was evaluated based in statistical comparisons of relevant pharmacokinetic parameters, obtained from data of drug concentrations in blood.

Study Overview

• Status: Completed
• Conditions: Skin Infections (Acne)
• Intervention / Treatment: Drug: Isotretinoin 40 mg; Drug: Isotretinoin 40 mg

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

Contacts and Locations

Study Locations

• Mexico
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64600
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

Male volunteers. Ages between 18 and 45 years old. BMI (Body Mass Index) between 20 to 26 kg/m2. Anti-doping tests negative results. Clinical biochemical test values: Hematic Biometry, Urine Analysis, Biochemical Profile: (Glucose, Ureic Nitrogen, Urea, Creatinine, Uric Acid, Cholesterol, Triglycerides, Total Proteins, Albumin, Globulin, Bilirubin (total, indirect and direct), Alkaline Phosphatase, Lactic Dehydrogenase, AST, ALT, Calcium, Phosphorus, Sodium, Potassium, Chlorine and Iron), Ac VIH, AgsHB and RPR (luetic test), must fall within an interval between minimum and maximum values in connection to said tests accepted values.

Normal Electrocardiogram and Chest X-rays. In exception cases, accepted may be a candidate for which any previously mentioned test is exceeded regarding considered valid maximum and minimum accepted normal values, as long as it involves an isolated value and there are no other manifestations which could allow assuming that a given value is related to a disease or is remnant of another. These cases must be approved by clinical area and declared as "Non-clinically significant".

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Exclusion Criteria:

Electrocardiographic Anomalies; radiological Anti-doping tests positive results, Positive results regarding RPR; VIH and AgsHB tests. Personal or family history of allergy to medication in question. Having any kind of allergy, since these persons are in higher risk of suffering from medicamentous allergy.

Tobacco use. Recreational drug use. Persons undergoing any medical treatment. Existence of concurrent or intercurrent disease. Existence of justified doubt regarding questionnaire answers truthfulness. Having participated in bioequivalence or bioavailability studies or having donated blood 2 months before the study.

Presence of clinically important gastrointestinal diseases or malabsorption history during the last year.

Presence of a medical condition requiring regular medication (with prescription or over-the- counter medication) with systemic absorption.

Narcotics or alcohol addiction history requiring treatment. Finally, excluded will be all those volunteers not meeting that established in Mexican Official Standard NOM-177-SSA1-1998.

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A(reference)/B(test); initial administration of reference and cross-over to test	Drug: Isotretinoin 40 mg; Roaccutan 2 capsules of 20 mg; reference drug; Other Names: Roaccutan; Productos Roche; Drug: Isotretinoin 40 mg; Oratane 2 capsules of 20 mg; test drug; Other Names: Oratane; Laboratorios Dermatologicos Darier SA de CV
Experimental: B(test)/A(reference); initial administration of test and cross-over to reference	Drug: Isotretinoin 40 mg; Roaccutan 2 capsules of 20 mg; reference drug; Other Names: Roaccutan; Productos Roche; Drug: Isotretinoin 40 mg; Oratane 2 capsules of 20 mg; test drug; Other Names: Oratane; Laboratorios Dermatologicos Darier SA de CV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Plasma Concentration (CMAX) of isotretinoin	pharmacokinetics	0.0, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10.0, 12.0, 16.0, 24.0, 36.0, 48.0, 60.0, 72.0 and 96.0 hours postdosage
Area under the plasma concentration versus time curve (AUC) of isotretionin	pharmacokinetics	0.0, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 7.0, 8.0, 10.0, 12.0, 16.0, 24.0, 36.0, 48.0, 60.0, 72.0 and 96.0 hours postdosage

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence od adverse events	Safety	20 days

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): August 26, 2011
• Primary Completion (Actual): September 23, 2011
• Study Completion (Actual): September 23, 2011

Study Registration Dates

• First Submitted: December 13, 2012
• First Submitted That Met QC Criteria: May 23, 2013
• First Posted (Estimate): May 29, 2013

Study Record Updates

• Last Update Posted (Actual): July 18, 2017
• Last Update Submitted That Met QC Criteria: July 13, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: pharmacokinetics; Mexico; bioequivalence; Isotretinoin
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Infections; Inflammation; Connective Tissue Diseases; Suppuration; Cellulitis; Skin Diseases, Infectious; Dermatologic Agents; Isotretinoin
• Other Study ID Numbers: 116615