A Study of Duloxetine Hydrochloride Hard Gelatinous Capsule Compared To Cymbalta

Study Overview
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Brief Summary
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In Brazil, duloxetine is currently available as hard gelatinous capsule with delayed release microgranules for oral administration containing enteric-coated pellets of 33.7, or 67.3 mg of duloxetine hydrochloride equivalent to 30 mg or 60 mg of duloxetine (Cymbalta®), respectively. The Sponsor has developed a hard gelatinous capsule with delayed release microgranules formulation containing enteric-coated pellets of 33.7, or 67.3 mg of duloxetine hydrochloride equivalent to 30, or 60 mg of duloxetine, respectively. The purpose of this study is to verify through a single dose study, if the test formulation of duloxetine (60 mg) is bioequivalent to the reference formulation (Cymbalta® 60 mg) when administered with the same dosage and under fasted conditions in healthy male research subjects.

Official Title
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A PHASE IV, SINGLE-DOSE, OPEN-LABEL, RANDOMIZED, 2-WAY CROSSOVER STUDY TO DETERMINE THE BIOEQUIVALENCE OF DULOXETINE HYDROCHLORIDE HARD GELATINOUS CAPSULE WITH DELAYED RELEASE MICROGRANULES (60 MG; PFIZER S.R.L - ARGENTINA) COMPARED WITH CYMBALTA(REGISTERED) ( 60 MG; ELI LILLY DO BRASIL LTDA) IN HEALTHY MALE RESEARCH SUBJECTS UNDER FASTED CONDITIONS

Conditions
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Healthy

Intervention / Treatment
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* Drug: Cymbalta Capsules
* Drug: Duloxetine Hydrochloride Capsules


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male research subjects who, at the time of screening, are between the ages of 18 and 55 years, inclusive. Body mass index (BMI) of 18.5 kg/m2 to 24.9 kg/m2, and a total body weight >50 kg (>110 lbs). Evidence of a personally signed and dated informed consent document indicating that the research subject has been informed of all pertinent aspects of the study. Research subjects that never smoked. Research subjects who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures. Exclusion Criteria: Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease. Clinically significant infections within the past 3 months, evidence of any infection within the past 7 days, history of disseminated herpes simplex infection or recurrent (>1 episode) or disseminated herpes zoster. Vaccination with live or attenuated vaccines within 6 weeks prior to dosing. A history of suicidal thoughts, behavior or suicide attempts. History of narrow angle glaucoma. Any condition possibly affecting drug absorption (eg, gastrectomy, colon resection, etc.). History of or current positive results for any of the following serological tests: hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), anti hepatitis C core antibody (HCV Ab), or human immunodeficiency virus (HIV) 1 and 2. Malignancy or a history of malignancy. A positive urine drug test. A positive alcohol screen. History of regular alcohol consumption exceeding 21 drinks/week for male research subjects [1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor] within 6 months before screening. Use of tobacco or all nicotine containing products. Treatment with an investigational drug within 6 months or 5 half lives preceding the first dose of investigational product (whichever is longer). Fertile male subjects who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 28 days after the last dose of investigational product. Use of prescription or nonprescription drugs and dietary supplements within 14 days or 5 half lives (whichever is longer) prior to the first dose of investigational product. Consumption of grapefruit or grapefruit related citrus fruits (eg, Seville oranges, pomelos) or juices within 7 days prior to dosing. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 3 months prior to screening until collection of the final PK blood sample (Period 2, Day 4). History of sensitivity to heparin or heparin induced thrombocytopenia. History of hypersensitivity to duloxetine or any of the components in the formulation of the study products. Unwilling or unable to comply with the criteria in the Lifestyle Requirements section of this protocol. Use of any medicinal product that is an inductor or strong inhibitor of CYP450 1A2 or 2D6 (eg, rifampicin, omeprazole, fluvoxamine, ciprofloxacin, fluoxetine, paroxetine, etc) within two weeks before administration of the investigational product and at any time during the study. Use of any medicinal product that inhibits monoamine oxidase A or B (eg, phenelzine, isocarboxacid, linezolid) within two weeks before administration of the investigational product and at any time during the study till at least 5 days after the last dose of investigational product.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Duloxetine Hydrochloride<br>Duloxetine hydrochloride hard gelatinous capsule 60 mg by mouth on Day 1 of period 1 or 2 | Drug: Duloxetine Hydrochloride Capsules<br>* Experimental Drug: Duloxetine hydrochloride - hard gelatinous capsule with delayed release microgranules (Pfizer S.R.L - Argentina.) equivalent to 60 mg of duloxetine.<br>* Other names: Test Drug;|
| Active Comparator: Cymbalta<br>Duloxetine hydrochloride hard gelatinous capsule 60 mg by mouth on Day 1 of period 1 or 2 | Drug: Cymbalta Capsules<br>* Active Comparator: Cymbalta®- hard gelatinous capsule with delayed release microgranules ( Eli Lilly do Brasil Ltda) equivalent to 60 mg of duloxetine.<br>* Other names: Reference Drug;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration-time curve | Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) | Up to 72 hours post dose | 
| Maximum plasma concentrations (Cmax) |  | Up to 72 hours post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration-time curve from time zero extrapolated to infinite time |  | Up to 72 hours post dose | 
| Time to first occurrence of Cmax (Tmax) |  | Up to 72 hours post dose | 
| Terminal phase rate constant (kel) |  | Up to 72 hours post dose | 
| Number Of Participants with Clinically Significant Change From Baseline In Vital Signs | Following parameters will be analyzed for examination of vital signs: systolic and diastolic blood pressure, pulse rate, and axillary temperature. | Baseline up to Day 28 after last dose of drug administration | 
| Number Of Participants With Clinically Significant Change From Baseline in Laboratory Tests | Pre-defined criteria will be established to identify the values of potential clinical importance for the following laboratory tests: hematology, serum chemistry, and urinalysis, and electrocardiograms (ECG). | Baseline up to Day 28 after last dose of drug administration |