Comparison of One Morphine Sulfate Sustained-Release 200mg Capsule With Two 100 mg KADIAN Capsules Under Fasting Conditions

Study Overview
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Brief Summary
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The objective of this single-dose, open-label, randomized, two-period crossover study was to compare the rate of absorption and oral bioavailability of a test formulation of morphine sulfate 200 mg sustained-release capsules manufactured by Alpharma Branded Products Division Inc. to an equivalent oral dose of the commercially available reference product, KADIAN 2 x 100 mg capsules manufactured by Alpharma Branded Products Division Inc. when administered after a 10-hour overnight fast.

Official Title
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A Single-Dose, 2-Period, 2-Treatment, 2-Way Crossover Study Comparing the Bioavailability of a Morphine Sulfate Sustained Release Capsule 1 x 200mg to KADIAN 2 x 100mg Capsules Under Fasting Conditions

Conditions
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Healthy

Intervention / Treatment
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* Drug: morphine sulfate sustained-release capsules
* Drug: KADIAN (morphine sulfate sustained-release) capsules


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must be a male or non-pregnant, non-breast-feeding female. Subject must be between 18 and 50 years of age inclusive. Subject's body weight should be within +/- 15% of the ideal body weight for their height and estimated frame based on the Metropolitan Life Insurance Company Table and weigh a minimum of 50 kg (110 lbs). Female subjects - not surgically sterile or at least two years postmenopausal - must agree to utilize one of the following forms of contraception, if sexually active with a male partner, from screening through completion of the study. Approved forms of contraception are abstinence, hormonal (oral, implant, transdermal or injection), double barrier (condom and diaphragm with spermicide), IUD, or vasectomized partner (6 months minimum). Subject must voluntarily consent to participate in this study and provide their written informed consent prior to completion of any study-specific procedures. Subject is willing and able to remain in the study unit for the entire duration of each confinement period and return to the study site for any outpatient visits. Exclusion Criteria: History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, oncologic or psychiatric disease or any other condition which, in the opinion of the Investigator would jeopardize the safety of the subject or the validity of the study results. Has a clinically significant abnormal finding on the physical exam, medical history or clinical laboratory results at screening. History or presence of allergic or adverse response to the study drug or related drugs. Has been on a significantly abnormal diet during the four weeks preceding the first dose of study medication. Has donated blood or plasma within 30 days prior to the first dose of study medication. Has participated in another clinical trial within 30 days prior to first dose of study medication. Has used any over-the-counter (OTC) medication including vitamins, within 7 days prior to the first dose of study medication without evaluation and approval by the study investigator. Has used any prescription medication, except hormonal contraceptive or hormonal replacement therapy, within 7 days prior to the first dose of study medication without evaluation and approval by the study investigator. Has been treated with any known enzyme altering drugs such as barbiturates, phenothiazines, cimetidine, carbamazepine, etc., within 30 days prior to the first dose of study medication. Has smoked or used tobacco products within 60 days prior to the first dose of study medication. Has a history of substance abuse (including alcohol) in the past 5 years. Is a female with a positive pregnancy test result. Has a positive urine screen for drugs of abuse (amphetamines, barbiturates, benzodiazepines, cocaine, cannabinoids, opiates). Has had a positive test for, or has been treated for hepatitis B, hepatitis C or HIV.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: 1<br>Treatment A (test product) followed by Treatment B (reference product) | Drug: morphine sulfate sustained-release capsules<br>* 1 x 200 mg, single-dose capsule<br>* Other names: Test product;Drug: KADIAN (morphine sulfate sustained-release) capsules<br>* 2 x 100 mg, single-dose capsule<br>* Other names: Reference product;|
| Other: 2<br>Treatment B (reference product) followed by Treatment A (test product) | Drug: morphine sulfate sustained-release capsules<br>* 1 x 200 mg, single-dose capsule<br>* Other names: Test product;Drug: KADIAN (morphine sulfate sustained-release) capsules<br>* 2 x 100 mg, single-dose capsule<br>* Other names: Reference product;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma Morphine Concentration |  | 0 (predose), and 2,4,6,6.5,7,7.5,8,8.5,9,9.5,10,12,18,24,30,36,48 hrs post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time of Maximum Plasma Morphine Concentration |  | 0 (predose), and 2,4,6,6.5,7,7.5,8,8.5,9,9.5,10,12,18,24,30,36,48 hrs post dose | 
| Area Under the Curve to the Last Measurable Time Point for Plasma Morphine |  | 0 (predose), and 2,4,6,6.5,7,7.5,8,8.5,9,9.5,10,12,18,24,30,36, 48 hrs post dose | 
| Area Under the Curve to Infinity for Plasma Morphine |  | 0 (predose), and 2,4,6,6.5,7,7.5,8,8.5,9,9.5,10,12,18,24,30,36,48 hrs post dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bioequivalence, morphine sulfate sustained release capsules, KADIAN capsules, 200 mg