Clinical trial NCT01100437: Safety Study to Assess Opiate Withdrawal Signs and Symptoms in Opioid Dependent Patients
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¿
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Chronic Pain
Keywords: opioid
morphine
naltrexone
withdrawal signs
withdrawal symptoms
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2010-04-09
Enrollment: 14
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER

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.

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 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.

Primary outcomes:
measure: Number of Participants With Clinical Opiate Withdrawal Scale (COWS) Score Greater Than or Equal to (≥) 13 in the Treatment Phase
timeFrame: 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:
measure: Average Numeric Pain Rating Scale (NPRS) in Titration/Stabilization and Maintenance Phases
timeFrame: Baseline up to Day 63
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) During the Treatment Phase
timeFrame: 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
measure: Maximum Observed Plasma Concentration (Cmax) During the Treatment Phase
timeFrame: 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
measure: Minimum Observed Plasma Concentration (Cmin) During the Treatment Phase
timeFrame: 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
measure: Apparent Oral Clearance (CL/F) During the Treatment Phase
timeFrame: 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
measure: Volume of Distribution (Vd/F)During the Treatment Phase
timeFrame: 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
measure: Plasma Decay Half-Life (t1/2) During the Treatment Phase
timeFrame: 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
measure: Area Under the Curve From Time Zero to End of Dosing Interval (AUC0-τ) During the Treatment Phase
timeFrame: 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
measure: Area Under the Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last) During the Treatment Phase
timeFrame: 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
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] During the Treatment Phase
timeFrame: 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:
measure: Time to First Occurrence of a COWS Score ≥ 13 for Each Treatment During the Treatment Phase
timeFrame: 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
measure: Morphine Plasma Concentration at First COWS ≥ 13 in the Treatment Phase
timeFrame: 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
measure: Naltrexone Plasma Concentration at First COWS ≥ 13 in the Treatment Phase
timeFrame: 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
measure: 6-β-Naltrexone Plasma Concentration at First COWS ≥ 13 in Treatment Phase
timeFrame: 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
measure: Maximum Post-dose COWS in the Treatment Phase
timeFrame: Between 0.5 and 24 hours post-dose
Locations:
city: Salt Lake City
country: United States
facility: Lifetree Clinical Research
state: Utah
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: 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.