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

Chronic Pain Clinical Trial

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¿

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01100437
• Other study ID #: ALO-01-09-111
• Secondary ID: B4541002
• Status: Terminated
• Phase: Phase 4
• First received: April 7, 2010
• Last updated: July 5, 2012
• Start date: April 2010
• Est. completion date: March 2011

Study information

• Verified date: November 2011
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 14
• Est. completion date: March 2011
• Est. primary completion date: March 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor)

Related Conditions & MeSH terms

• Chronic Pain
• Signs and Symptoms

Intervention

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
• 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

Locations

Country	Name	City	State
United States	Lifetree Clinical Research	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	Yes
Secondary	Average Numeric Pain Rating Scale (NPRS) in Titration/Stabilization and Maintenance Phases	Average pain scores in the previous 24 hours using an 11 point NPRS ranging from no pain (0) to worst pain (10).	Baseline up to Day 63	No
Secondary	Time to Reach Maximum Observed Plasma Concentration (Tmax) During the Treatment Phase	Average Tmax for Morphine, Naltrexone and 6-ß-Naltrexol	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	No
Secondary	Maximum Observed Plasma Concentration (Cmax) During the Treatment Phase	Average Cmax for Morphine, Naltrexone and 6-ß-Naltrexol	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	No
Secondary	Minimum Observed Plasma Concentration (Cmin) During the Treatment Phase	Average Cmin for Morphine, Naltrexone and 6-ß-Naltrexol	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	No
Secondary	Apparent Oral Clearance (CL/F) During the Treatment Phase	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.	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	No
Secondary	Volume of Distribution (Vd/F)During the Treatment Phase	Average Vd/F for Morphine, Naltrexone and 6-ß-Naltrexol	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	No
Secondary	Plasma Decay Half-Life (t1/2) During the Treatment Phase	Average plasma decay half-life of morphine, naltrexone and 6-ß-Naltrexol. Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.	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	No
Secondary	Area Under the Curve From Time Zero to End of Dosing Interval (AUC0-t) During the Treatment Phase	Average AUC0-t for Morphine, Naltrexone and 6-ß-Naltrexol reported. t=24 hours	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	No
Secondary	Area Under the Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last) During the Treatment Phase	Average AUC0-last for Morphine, Naltrexone and 6-ß-Naltrexol. Area under the plasma concentration time-curve from time zero to the last measured concentration.	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	No
Secondary	Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)] During the Treatment Phase	AUC (0 - 8)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - 8). It is obtained from AUC (0 - t) plus AUC (t - 8). Average AUC 0-8 for Morphine, Naltrexone and 6-ß-Naltrexol reported.	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	No

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