Comparison of KADIAN 100 mg When Dosed With Alcohol Under Fasting and Fed Conditions Compared to Water

The objective of this study was to compare the single-dose relative bioavailability of Alpharma Branded Products Division Inc. (KADIAN) 100 mg morphine sulfate extended-release capsules when dosed with alcohol under fasting and fed conditions compared to water.

In addition, the pharmacokinetics of an immediate release solution following a 20 mg dose was assessed for informational purposes and for possible modeling.

• Other: KADIAN + Ethanol
  Capsules 100 mg + 240 mL 40% ethanol in 4 shots of 60 mL
• Other: KADIAN + Water
  Capsules 100mg + 240 mL in 4 shots of 60 mL
• Other: morphine sulfate IR oral solution + water
  Solution 20mg/5mL, 235 mL of water in 1 shot of 55 mL (+ 5mL IR morphine) + 3 shots of 60 mL of water

• Experimental: 1
  KADIAN Capsule + alcohol (under fasting conditions)
  Intervention: Other: KADIAN + Ethanol
• Experimental: 2
  KADIAN Capsule + alcohol (under fed conditions)
  Intervention: Other: KADIAN + Ethanol
• Experimental: 3
  KADIAN Capsule + water (under fasting conditions)
  Intervention: Other: KADIAN + Water
• Experimental: 4.
  Morphine sulfate IR oral solution + water (under fasting conditions)
  Intervention: Other: morphine sulfate IR oral solution + water

Inclusion Criteria:

• Healthy adult male volunteers, 21 to 40 years of age.
• Subjects were non-smokers for at least 3 months or light smokers (less than 10 pack-years).
• Subjects with a history of moderate consumption of at least 7-21 units of alcohol per week or the alcohol equivalent (12 oz beer = 5 oz of 80-proof distilled spirits = 1 unit).
• Weighing at least 70 kg and within 20% of their ideal weights (table of "Desirable Weights of Adults", Metropolitan Life Insurance Company, 1983).
• Medically healthy subjects with no clinically significant abnormalities in their laboratory profile and ECGs, as deemed by the Principal Investigator.
• Voluntarily consented to participate in the study.

Exclusion Criteria:

• History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease.
• In addition, history or presence of: alcoholism or drug abuse; asthma or other chronic respiratory illness; diabetes; gastrointestinal dysmotility, irritable bowel syndrome, chronic constipation or recent enteritis; hypersensitivity or idiosyncratic reaction to morphine or other opioids; hypersensitivity or idiosyncratic reaction to naltrexone, naloxone, or other opioids antagonists.
• History of no alcohol intake (alcohol-naive) or less than moderate alcohol intake.
• Subject with a history of alcohol intake exceeding the equivalence of 21 units/week or exceeding the average of 3 drinks per day.
• Subjects who had a surgery of the gastrointestinal tract (except appendectomy) which would interfere with absorption of the study drug.
• Subjects who received hepatic enzyme inducing drugs (e.g. Nizoral, Tagamet) within the previous three months.
• Subjects whose QTc interval was >450 msec at screening and prior to dosing.
• Subjects whose sitting blood pressure was less than 110/45 mm Hg at screening or 100/45 mm Hg before dosing.
• Subjects who had been on a special diet (for whatever reason) during the 28 days prior to the first dose and throughout the study.
• Subjects who had made any significant donation or loss of blood within 56 days.
• Subjects who had made a plasma donation within 7 days prior to the study.
• Subjects with hemoglobin less than 12.0 g/dL.
• Subjects who had participated in another clinical trial within 28 days prior to the first dose.
• Subjects who had a positive urine test for drugs of abuse or alcohol.
• Subjects who had a positive test for, or had been treated for hepatitis B, hepatitis C or HIV.