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

NCT01100437 | Terminated Phase 4 Results

• 2 other identifiers: ALO-01-09-111B4541002
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Chronic Pain

Keywords

opioid; morphine; naltrexone; withdrawal signs; withdrawal symptoms

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Clinical Opiate Withdrawal Scale (COWS) Score Greater Than or Equal to (≥) 13 in the Treatment Phase

  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).

  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)

Secondary Outcomes (10)

• Average Numeric Pain Rating Scale (NPRS) in Titration/Stabilization and Maintenance Phases

  Baseline up to Day 63

• Time to Reach Maximum Observed Plasma Concentration (Tmax) During the Treatment Phase

  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

• Maximum Observed Plasma Concentration (Cmax) During the Treatment Phase

  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

• Minimum Observed Plasma Concentration (Cmin) During the Treatment Phase

  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

• Apparent Oral Clearance (CL/F) During the Treatment Phase

  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

Other Outcomes (5)

• Time to First Occurrence of a COWS Score ≥ 13 for Each Treatment During the Treatment Phase

  Prior to dose, 0, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 24 hr post-dose and UA

• Morphine Plasma Concentration at First COWS ≥ 13 in the Treatment Phase

  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

• Naltrexone Plasma Concentration at First COWS ≥ 13 in the Treatment Phase

  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

Study Arms (2)

EMBEDA™ (morphine sulfate/naltrexone hydrochloride) crush

EXPERIMENTAL

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

EMBEDA™ (morphine sulfate/naltrexone hydrochloride) whole

EXPERIMENTAL

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

Interventions

EMBEDA™ (morphine sulfate/naltrexone hydrochloride) crush DRUG

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

EMBEDA™ (morphine sulfate/naltrexone hydrochloride) crush

EMBEDA™ (morphine sulfate/naltrexone hydrochloride) whole DRUG

EMBEDA capsules, administered orally and intact at each patient's stable dose, given either once daily or twice daily with 150mL placebo solution

EMBEDA™ (morphine sulfate/naltrexone hydrochloride) whole

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

Lifetree Clinical Research

Salt Lake City, Utah, 84106, United States

Location

Related Publications (1)

• Setnik B, Roland CL, Goli V, Sommerville K, Webster L. A clinical trial to determine if corelease of morphine and naltrexone from crushed extended-release capsules induces withdrawal in opioid-dependent patients: a descriptive analysis of six patients. J Opioid Manag. 2013 Mar-Apr;9(2):139-50. doi: 10.5055/jom.2013.0155.

  PMID: 23709323 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Chronic Pain; Substance Withdrawal Syndrome

Interventions

morphine, naltrexone combination; Morphine; Naltrexone

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Naloxone

Limitations and Caveats

Sponsor terminated study early on 10-Mar-2011.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 7, 2010
• First Posted: April 9, 2010
• Study Start: April 1, 2010
• Primary Completion: March 1, 2011
• Study Completion: March 1, 2011
• Last Updated: July 13, 2012
• Results First Posted: March 28, 2012

Record last verified: 2011-11

Locations

US (1)