Safety Study to Assess Opiate Withdrawal Signs and Symptoms in Opioid Dependent Patients

This study has been terminated.
(See termination reason in detailed description.)
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01100437
First received: April 7, 2010
Last updated: July 5, 2012
Last verified: November 2011
  Purpose

This study will evaluate whether crushed EMBEDA capsules induce clinical opiate withdrawal signs and symptoms in opioid-dependent patients with chronic non-cancer pain who are stabilized on EMBEDA.


Condition Intervention Phase
Chronic Pain
Drug: EMBEDA™ (morphine sulfate/naltrexone hydrochloride) crush
Drug: EMBEDA™ (morphine sulfate/naltrexone hydrochloride) whole
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Official Title: A Single-Center, Randomized, Double-Blind, Two-Way Crossover Study to Evaluate Whether a Single-Dose Administration of Crushed and Whole EMBEDA Induces Clinical Opiate Withdrawal Signs and Symptoms in Opioid-Dependent Patients With Chronic, Non-Cancer Pain Who Are Stabilized on EMBEDA¿

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Number of Participants With Clinical Opiate Withdrawal Scale (COWS) Score Greater Than or Equal to (≥) 13 in the Treatment Phase [ Time Frame: Prior to dose, 0, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 24 hours (hr) post-dose and unscheduled assessment (UA) ] [ Designated as safety issue: Yes ]
    COWS is an 11 section clinical assessment of withdrawal symptoms, each section is rated from 0 (no symptom) to 4 or 5 (most severe symptom). Total score is classified into a 4 point rating scale (mild 5-12, moderate 13-24, moderately severe 25-36 and severe more than 36 points).


Secondary Outcome Measures:
  • Average Numeric Pain Rating Scale (NPRS) in Titration/Stabilization and Maintenance Phases [ Time Frame: Baseline up to Day 63 ] [ Designated as safety issue: No ]
    Average pain scores in the previous 24 hours using an 11 point NPRS ranging from no pain (0) to worst pain (10).

  • Time to Reach Maximum Observed Plasma Concentration (Tmax) During the Treatment Phase [ Time Frame: Prior to dose, 0, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, and 24 hr post-dose ] [ Designated as safety issue: No ]
    Average Tmax for Morphine, Naltrexone and 6-β-Naltrexol

  • Maximum Observed Plasma Concentration (Cmax) During the Treatment Phase [ Time Frame: Prior to dose, 0, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, and 24 hr post-dose ] [ Designated as safety issue: No ]
    Average Cmax for Morphine, Naltrexone and 6-β-Naltrexol

  • Minimum Observed Plasma Concentration (Cmin) During the Treatment Phase [ Time Frame: Prior to dose, 0, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, and 24 hr post-dose ] [ Designated as safety issue: No ]
    Average Cmin for Morphine, Naltrexone and 6-β-Naltrexol

  • Apparent Oral Clearance (CL/F) During the Treatment Phase [ Time Frame: Prior to dose, 0, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, and 24 hr post-dose ] [ Designated as safety issue: No ]
    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

  • Volume of Distribution (Vd/F)During the Treatment Phase [ Time Frame: Prior to dose, 0, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, and 24 hr post-dose ] [ Designated as safety issue: No ]
    Average Vd/F for Morphine, Naltrexone and 6-β-Naltrexol

  • Plasma Decay Half-Life (t1/2) During the Treatment Phase [ Time Frame: Prior to dose, 0, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, and 24 hr post-dose ] [ Designated as safety issue: No ]
    Average plasma decay half-life of morphine, naltrexone and 6-β-Naltrexol. Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

  • Area Under the Curve From Time Zero to End of Dosing Interval (AUC0-τ) During the Treatment Phase [ Time Frame: Prior to dose, 0, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, and 24 hr post-dose ] [ Designated as safety issue: No ]
    Average AUC0-τ for Morphine, Naltrexone and 6-β-Naltrexol reported. τ=24 hours

  • Area Under the Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last) During the Treatment Phase [ Time Frame: Prior to dose, 0, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, and 24 hr post-dose ] [ Designated as safety issue: No ]
    Average AUC0-last for Morphine, Naltrexone and 6-β-Naltrexol. Area under the plasma concentration time-curve from time zero to the last measured concentration.

  • Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] During the Treatment Phase [ Time Frame: Prior to dose, 0, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, and 24 hr post-dose ] [ Designated as safety issue: No ]
    AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞). Average AUC 0-∞ for Morphine, Naltrexone and 6-β-Naltrexol reported.


Enrollment: 14
Study Start Date: April 2010
Study Completion Date: March 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: EMBEDA™ (morphine sulfate/naltrexone hydrochloride) crush
EMBEDA (morphine sulfate plus naltrexone hydrochloride ER) capsules crushed and mixed in solution and administered orally at each patient's stable dose, given either once daily or twice daily.
Drug: EMBEDA™ (morphine sulfate/naltrexone hydrochloride) crush
Placebo capsules plus EMBEDA capsules crushed and mixed in solution administered orally at each patient's stable dose, given either once daily or twice daily
Experimental: EMBEDA™ (morphine sulfate/naltrexone hydrochloride) whole
EMBEDA (morphine sulfate plus naltrexone hydrochloride ER) capsules, administered orally and intact at each patient's stable dose, given either once daily or twice daily
Drug: EMBEDA™ (morphine sulfate/naltrexone hydrochloride) whole
EMBEDA capsules, administered orally and intact at each patient's stable dose, given either once daily or twice daily with 150mL placebo solution

Detailed Description:

The decision to terminate the trial was due to a lack of study drug supply. Decision was not based on any safety concerns. The date of the notification of termination letter was March 11, 2011.

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Chronic moderate to severe non-cancer pain that has been treated with opioid analgesics for at least three months (with stabilized pain control and stabilized dose for 28 days prior to enrollment).
  • Receiving an opioid dose equivalent to 20 mg - 120 mg morphine once or twice daily.
  • Patient displays signs and symptoms of withdrawal (i.e., COWS score ≥5) following naloxone administration during the Naloxone Challenge.

If female and able to become pregnant, must use an approved method of birth control.

  • Excluding the chronic moderate to severe non-cancer pain, the patient is judged by the Investigator to be in generally good health at screening based upon the results of a medical history, physical examination, laboratory profile, and 12 lead electrocardiogram (ECG).

Exclusion Criteria:

  • Female who is pregnant or breastfeeding.
  • Patient has a known allergy or history of significant adverse reaction to morphine, other opioids, naltrexone, acetaminophen, or related compounds.
  • Patient is receiving systemic chemotherapy, has an active malignancy of any type, or has been diagnosed with cancer within the 5 years prior to screening (excluding squamous or basal cell carcinoma of the skin).
  • History of, or ongoing, alcohol or drug abuse.
  • Patient has made a donation of blood or has had a significant blood loss within 30 days prior to screening.
  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.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01100437

Locations
United States, Utah
Lifetree Clinical Research
Salt Lake City, Utah, United States, 84106
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided by Pfizer

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01100437     History of Changes
Other Study ID Numbers: ALO-01-09-111, B4541002
Study First Received: April 7, 2010
Results First Received: February 27, 2012
Last Updated: July 5, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
opioid
morphine
naltrexone
withdrawal signs
withdrawal symptoms

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

ClinicalTrials.gov processed this record on July 26, 2014