Bioequivalence Study of Morphine Sulfate 60 mg Extended-Release Tablets Under Fed Conditions

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Ranbaxy Inc.
ClinicalTrials.gov Identifier:
NCT01665209
First received: August 13, 2012
Last updated: NA
Last verified: August 2012
History: No changes posted
  Purpose

The study was to evaluate the relative bioavailability of morphine and morphine-6-glucuronide from 2 tablet products and determine if the 2 products were bioequivalent to each other.


Condition Intervention Phase
Healthy
Drug: Morphine Sulfate
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Crossover Assignment
Masking: Open Label
Official Title: Single Dose Two-Way Crossover Fed Bioequivalence Study of Morphine Sulfate 60 mg Extended-Release Tablets in Healthy Volunteers.

Resource links provided by NLM:


Further study details as provided by Ranbaxy Inc.:

Primary Outcome Measures:
  • Composite of Pharmacokinetics [ Time Frame: predose and at 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.333, 3.667, 4, 5, 6, 8, 10, and 12 hours post-dose ] [ Designated as safety issue: No ]
    Cmax, Area Under Curve and Tmax


Enrollment: 24
Study Start Date: October 2006
Study Completion Date: December 2006
Primary Completion Date: October 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Morphine Sulfate 60mg Extended-release tablets
A single oral dose of Morphine Sulfate 60mg Extended-release tablets of Ohm Laboratories Inc.
Drug: Morphine Sulfate
Morphine Sulfate 60mg Extended-release tablets
Active Comparator: MS Contin® 60 mg Controlled-release tablets
A single oral dose of MS Contin® 60 mg Controlled-release tablets of Purdue Pharma L.P.
Drug: Morphine Sulfate
Morphine Sulfate 60mg Extended-release tablets

Detailed Description:

This was a single center, single-dose, randomized, open-label, two-treatment, two-period crossover bioequivalence study designed to evaluate the pharmacokinetics and bioequivalence of morphine sulfate formulations under fed conditions. Normal healthy males and females at least 18 years of age were screened for enrollment into the trial.

Potential subjects who met the eligibility criteria randomly received either oral Morphine Sulfate 60 mg Extended-release tablets or oral MS Contin® 60 mg Controlled-release tablets on Day 1 in Period 1, then, following the washout period, they were dosed on Day 8 in Period 2 with the other treatment. There was a 7-day washout period between dosing. The study drug treatments were administered following the Food and Drug Administration (FDA) high-fat breakfast, which was served after subjects had been fasting for 11 hours. Fasting resumed until 4 hours post-dose for both treatment groups. All enrolled subjects were administered single oral doses of 50 mg of naltrexone hydrochloride 10 hours predose, 1 hour predose, and 12 hours post-dose of the study drug treatment on Day -1 and Day 1 in Period 1 and on Day 7 and Day 8 in Period 2. Potential subjects (ie, alternates) were administered single oral doses of 50 mg of naltrexone hydrochloride 10 hours predose and 1 hour predose of the study drug treatment on Day -1 and Day 1 in Period 1.

Subjects visited the clinic at Screening (within 28 days prior to dosing) to assess eligibility and returned to the clinic on Day -1 for the Period 1 confinement period that lasted through Day 2. To complete Period 1, subjects were to return on Day 3 for the collection of pharmacokinetic blood samples. Period 1 dosing was followed by the 7-day washout period. Subjects returned to the clinic for the Period 2 confinement period on Day 7, which continued through Day 9. To complete Period 2, subjects were to return on Day 10 in that period for the collection of pharmacokinetic and safety blood samples.

Pharmacokinetic and safety assessments were performed during the conduct of the trial. Blood samples for the evaluation of morphine and morphine-6-glucuronide plasma concentrations were obtained while subjects were at the clinic and after discharge, as appropriate. Pharmacokinetic samples were collected over a 48-hour period of time following administration of the study drug treatment.

Medical care of the subjects was assured by the presence of a physician for at least 4 hours post-dose, and the physician remained on-call to treat adverse events (AEs). Professional medical personnel were on-site during the entire study confinement period. Adverse event information elicited during confinement at the clinic or during telephone contacts was reviewed and documented.

  Eligibility

Ages Eligible for Study:   19 Years to 41 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

For inclusion into the trial, subjects were required to fulfill all of the following criteria:

  1. Healthy subjects at least 18 years of age.
  2. Willingness to provide written informed consent after being informed of the nature of the study.
  3. Body mass index (BMI) between 18 and 30 and a weight of at least 110 pounds.
  4. Good health as determined by a lack of clinically significant abnormalities in health assessments performed at Screening, as judged by the physician.

Exclusion Criteria:

ny of the following was regarding as a criterion for excluding subjects from the trial:

  1. Hypersensitivity to morphine sulfate (MS Contin®), naltrexone (ReVia®), or related compounds.
  2. Conditions that affected the absorption, metabolism, or passage of drugs out of the body (eg, sprue, celiac disease, Crohn's disease, colitis, liver, kidney, or thyroid conditions).
  3. Recent history (within 1 year) of mental illness, drug addiction, drug abuse, or alcoholism.
  4. A hematocrit value of ≤ 33.0% for females and ≤ 37.0% for males.
  5. Donation of > 500 mL of blood in the past 8 weeks prior to study drug dosing or difficulty in donating blood.
  6. Receipt of an investigational drug within the 4 weeks prior to study drug dosing.
  7. Current use of any systemic prescription medications, except for oral/cutaneous/vaginal/injectable hormone contraceptives, within the 7 days prior to study drug dosing or over-the-counter (OTC) medication within 3 days of study drug dosing.

    This prohibition did not include vitamins or herbal preparations taken as nutritional supplements for non-therapeutic indications, as judged by the attending physician.

    Any nonprescription medication consumption reported was to be reviewed by the investigator prior to dosing. At the discretion of the investigator, these volunteers could be enrolled if the medication was not anticipated to alter study integrity or the safety of the subject.

  8. Regular smoking of more than 5 cigarettes weekly or the regular daily use of nicotine containing products beginning 3 months before study drug administration through the final evaluation.

    Subjects had to be able to refrain from smoking while confined in the clinic.

  9. Female subjects who were lactating or had a positive pregnancy test at Screening and prior to each of the treatment periods.

    Females were to use a medically acceptable method of contraception throughout the entire study period and for 1 week after study completion. Medically acceptable methods of contraception that could have been used by the subject and/or her partner were oral contraceptives/patches, progestin injection or implants, condom with spermicide, diaphragm with spermicide, intrauterine device (IUD), vaginal spermicidal or hormonal suppository, surgical sterilization of themselves or their partner(s), or abstinence. Females using contraceptive medications/devices must have used them consistently for at least 3 months prior to receiving study drug.

  10. Alcohol, grapefruit beverages or foods, caffeine, or xanthine beverages or foods beginning 48 hours before each study drug administration through the last pharmacokinetic (PK) sample of each treatment period.

    Such restricted items included coffee, tea, iced tea, Coke®, Pepsi®, Mountain Dew®, chocolate, brownies, etc.

  11. Regular use of any drugs known to induce or inhibit hepatic drug metabolism (examples include barbiturates, carbamazepine, rifampin, phenylhydantoins, phenothiazines, cimetidine, omeprazole, macrolides, imidazoles, fluoroquinolones) within 30 days prior to study drug administration.
  12. Positive test results for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), and hepatitis C antibody at Screening.
  13. Positive test results for drugs of abuse or pregnancy at Screening and prior to each study drug dosing period.
  14. Subjects having emesis after either dose of naltrexone administered prior to the study drug were not to be continued in the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

Additional Information:
No publications provided

Responsible Party: Ranbaxy Inc.
ClinicalTrials.gov Identifier: NCT01665209     History of Changes
Other Study ID Numbers: AAI-US-455
Study First Received: August 13, 2012
Last Updated: August 13, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Morphine
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 31, 2014