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

July 5, 2012 updated by: Pfizer

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¿

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
14

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Utah
      • Salt Lake City, Utah, United States, 84106
        • Lifetree Clinical Research

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

21 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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)
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Average Numeric Pain Rating Scale (NPRS) in Titration/Stabilization and Maintenance Phases
Time Frame: Baseline up to Day 63
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
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
Average Tmax for Morphine, Naltrexone and 6-β-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
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
Average Cmax for Morphine, Naltrexone and 6-β-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
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
Average Cmin for Morphine, Naltrexone and 6-β-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
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
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
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
Average Vd/F for Morphine, Naltrexone and 6-β-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
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
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.
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
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
Average AUC0-τ for Morphine, Naltrexone and 6-β-Naltrexol reported. τ=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
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
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.
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
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
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.
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 Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Time to First Occurrence of a COWS Score ≥ 13 for Each Treatment 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, 24 hr post-dose and UA
Average time to first occurrence of a COWS score ≥ 13
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
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
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
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
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
6-β-Naltrexone Plasma Concentration at First COWS ≥ 13 in 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
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 Post-dose COWS in the Treatment Phase
Time Frame: Between 0.5 and 24 hours post-dose
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).
Between 0.5 and 24 hours post-dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Pfizer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2010

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2011

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2011

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 7, 2010

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 7, 2010

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 9, 2010

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 13, 2012

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 5, 2012

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ALO-01-09-111
  • B4541002

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