Chronic PainPhase 4NCT01100437
Safety Study to Assess Opiate Withdrawal Signs and Symptoms in Opioid Dependent Patients
A Phase 4 study testing EMBEDA™ (morphine sulfate/naltrexone hydrochloride) crush and EMBEDA™ (morphine sulfate/naltrexone hydrochloride) whole in people with Chronic Pain, run by Pfizer at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Chronic Pain
- What is being tested?
- EMBEDA™ (morphine sulfate/naltrexone hydrochloride) crush and EMBEDA™ (morphine sulfate/naltrexone hydrochloride) whole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2010to Mar 2011
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Lifetree Clinical Research
Salt Lake City, Utah, 84106
About this study
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¿
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.
Read the 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.
- Conditions
- Chronic Pain
- Being tested
- EMBEDA™ (morphine sulfate/naltrexone hydrochloride) crush, EMBEDA™ (morphine sulfate/naltrexone hydrochloride) whole
- Keywords
- opioid, morphine, naltrexone, withdrawal signs, withdrawal symptoms
- Medical subject headings
- Chronic Pain, Substance Withdrawal Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EMBEDA™ (morphine sulfate/naltrexone hydrochloride) crushDrug
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) wholeDrug
EMBEDA capsules, administered orally and intact at each patient's stable dose, given either once daily or twice daily with 150mL placebo solution
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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 Receives: Drug: EMBEDA™ (morphine sulfate/naltrexone hydrochloride) whole |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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
Average pain scores in the previous 24 hours using an 11 point NPRS ranging from no pain (0) to worst pain (10).
Measured: Baseline up to Day 63
Time to Reach Maximum Observed Plasma Concentration (Tmax) During the Treatment Phase
Average Tmax for Morphine, Naltrexone and 6-β-Naltrexol
Measured: 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
Average Cmax for Morphine, Naltrexone and 6-β-Naltrexol
Measured: 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
Average Cmin for Morphine, Naltrexone and 6-β-Naltrexol
Measured: 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
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.
Measured: 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
Average Vd/F for Morphine, Naltrexone and 6-β-Naltrexol
Measured: 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
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.
Measured: 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
Average AUC0-τ for Morphine, Naltrexone and 6-β-Naltrexol reported. τ=24 hours
Measured: 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
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.
Measured: 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
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.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Apr 2010 (estimated)
- Study startApr 2010
- Primary completionMar 2011
- Study completionMar 2011
Why it stopped: See termination reason in detailed description.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic PainStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01100437
- Sponsor's protocol ID
- ALO-01-09-111
- Other IDs
- B4541002
- Status last verified
- Nov 2011
- First submitted
- 7 Apr 2010
- Last updated
- 13 Jul 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 23709323
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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¿
- ClinicalTrials.gov ID
- NCT01100437
- Acronym / sponsor ID
- ALO-01-09-111
- Conditions
- Chronic Pain
- Keywords
- opioid, morphine, naltrexone, withdrawal signs, withdrawal symptoms
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: See termination reason in detailed description.
- Enrolment
- 14 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- Apr 2010
- Primary completion
- Mar 2011 (actual)
- Study completion
- Mar 2011 (actual)
- First posted
- 9 Apr 2010 (estimated)
- Results
- Posted 28 Mar 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| EMBEDA™ (morphine sulfate/naltrexone hydrochloride) crush | Experimental | Drug: EMBEDA™ (morphine sulfate/naltrexone hydrochloride) crushEMBEDA (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. |
| EMBEDA™ (morphine sulfate/naltrexone hydrochloride) whole | Experimental | Drug: EMBEDA™ (morphine sulfate/naltrexone hydrochloride) wholeEMBEDA (morphine sulfate plus naltrexone hydrochloride ER) capsules, administered orally and intact at each patient's stable dose, given either once daily or twice daily |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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).
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EMBEDA™ (morphine sulfate/naltrexone hydrochloride) crushPlacebo capsules plus EMBEDA capsules crushed and mixed in solution 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) wholeEMBEDA capsules, administered orally and intact at each patient's stable dose, given either once daily or twice daily with 150mL placebo solution | Drug | EMBEDA™ (morphine sulfate/naltrexone hydrochloride) whole |
Primary outcome
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).
10 secondary outcomes
Average Numeric Pain Rating Scale (NPRS) in Titration/Stabilization and Maintenance Phases
Time frame: 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
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
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
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
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
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
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
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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jul 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 23709323Setnik 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.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pfizer CT.gov Call Center study director
Pfizer
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing EMBEDA™ (morphine sulfate/naltrexone hydrochloride) crush and EMBEDA™ (morphine sulfate/naltrexone hydrochloride) whole in people with Chronic Pain, run by Pfizer at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Jul 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Mar 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01100437, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jul 2012.