Clinical trial NCT00768183: Comparison of KADIAN 100 mg When Dosed With Alcohol Under Fasting and Fed Conditions Compared to Water
Official title: Phase 1, Single-Center, Open-label, Drug Interaction Study to Evaluate the Effect of Alcohol on the PK of Morphine Sulfate ER (KADIAN) Capsules in Healthy Adults Under Fasting and Fed Conditions and Relative BA to Morphine Solution
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: KADIAN
morphine
alcohol
water
solution
fed
fasting
Lead sponsor: Actavis Inc.
Sponsor class: INDUSTRY
First posted: 2008-10-07
Enrollment: 32
Sex: MALE
Minimum age (years): 21
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

Detailed description: This study was to evaluate the effect of consumming alcohol on the pharmacokie and bioavailability of Alpharma Branded Products Division Inc. (KADIAN) 100 mg morphine sulfate extended-release capsules under fasting and fed conditions.

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

Eligibility criteria: 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.

Primary outcomes:
measure: To evaluate the effect of alcohol ingestion on the pharmacokinetics of KADIAN
timeFrame: up to 48 hours post dosing
Secondary outcomes:
measure: To evaluate the pharmacokinetics assessment of an immediate release morphine solution following a 20 mg dose
timeFrame: up to 24 hours post dosing
Other outcomes:
Locations:
city: Lincoln
country: United States
facility: MDS Pharma Services
state: Nebraska
Study officials:
affiliation: MDS Pharma Services
name: James C Kisicki, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Johnson F, Wagner G, Sun S, Stauffer J. Effect of concomitant ingestion of alcohol on the in vivo pharmacokinetics of KADIAN (morphine sulfate extended-release) capsules. J Pain. 2008 Apr;9(4):330-6. doi: 10.1016/j.jpain.2007.11.009. Epub 2008 Jan 16.