Phase 1
N=80
Abuse Potential of Orally Administered Crushed Embeda Compared to Crushed Controlled-Release Morphine and Placebo in Non-Dependent Recreational Opioid Users
Nondependent Opioid Abuse, Episodic
Bottom Line
View on ClinicalTrials.gov: NCT01380093 ↗Enrolled (actual)
80
Serious AEs
0.4%
Results posted
May 2012
Primary outcome: Primary: Drug Liking: Area Under Effect Curve (AUE) From 0-2 Hours — 88.3; 100.3; 124.7 hrs*mm — p=<0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Placebo (Drug); MS Contin (morphine sulfate, controlled release) (Drug); EMBEDA (morphine sulfate / naltrexone hydrochloride) (Drug)
- Age
- Adult · 18+ yrs
- Sex
- All
- Sponsor
- Pfizer
- Primary completion
- May 2011
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Drug Liking: Area Under Effect Curve (AUE) From 0-2 Hours |
88.3; 100.3; 124.7 | <0.0001 sig |
| PRIMARY Drug Liking: Peak Effect (Emax) |
51.6; 65.2; 80.6 | <0.0001 sig |
| PRIMARY High: Area Under Effect Curve (AUE) From 0-2 Hours |
2.0; 26.9; 77.5 | <0.0001 sig |
| PRIMARY High: Peak Effect (Emax) |
1.8; 29.2; 64.1 | <0.0001 sig |
| SECONDARY Drug Liking: Area Under Effect Curve (AUE) From 0-1 Hour |
37.8; 43.1; 51.8 | <0.0001 sig |
| SECONDARY Drug Liking: Area Under Effect Curve (AUE) From 0-4 Hours |
188.6; 217.9; 265.6 | <0.0001 sig |
| SECONDARY Drug Liking: Area Under Effect Curve (AUE) From 0-8 Hours |
390.3; 447.3; 514.4 | <0.0001 sig |
| SECONDARY Drug Liking: Area Under Effect Curve (AUE) From 0-12 Hours |
591.0; 658.2; 732.9 | 0.0001 sig |
| SECONDARY Drug Liking: Area Under Effect Curve (AUE) From 0-24 Hours |
1192.1; 1263.0; 1348.2 | 0.0011 sig |
| SECONDARY Drug Liking: Time to Maximum (Peak) Effect (TEmax) |
5.8; 4.8; 2.7 | 0.1254 |
| SECONDARY High: Area Under Effect Curve (AUE) From 0-1 Hour |
0.9; 10.3; 25.5 | <0.0001 sig |
| SECONDARY High: Area Under Effect Curve (AUE) From 0-4 Hours |
3.4; 63.6; 178.9 | <0.0001 sig |
| SECONDARY High: Area Under Effect Curve (AUE) From 0-8 Hours |
6.5; 129.5; 330.5 | <0.0001 sig |
| SECONDARY High: Area Under Effect Curve (AUE) From 0-12 Hours |
8.1; 160.7; 412.3 | <0.0001 sig |
| SECONDARY High: Area Under Effect Curve (AUE) From 0-24 Hours |
10.7; 180.3; 485.4 | <0.0001 sig |
| SECONDARY High: Time to Maximum (Peak) Effect (TEmax) |
0.8; 2.7; 2.5 | 0.5607 |
| SECONDARY Good Effects: Area Under Effect Curve (AUE) From 0-1 Hour |
0.8; 12.2; 27.2 | <0.0001 sig |
| SECONDARY Good Effects: Area Under Effect Curve (AUE) From 0-2 Hours |
1.8; 30.4; 77.4 | <0.0001 sig |
| SECONDARY Good Effects: Area Under Effect Curve (AUE) From 0-4 Hours |
3.1; 70.5; 178.5 | <0.0001 sig |
| SECONDARY Good Effects: Area Under Effect Curve (AUE) From 0-8 Hours |
6.2; 141.2; 330.0 | <0.0001 sig |
| SECONDARY Good Effects: Area Under Effect Curve (AUE) From 0-12 Hours |
7.8; 174.6; 417.4 | <0.0001 sig |
| SECONDARY Good Effects: Area Under Effect Curve (AUE) From 0-24 Hours |
10.2; 196.0; 503.8 | <0.0001 sig |
| SECONDARY Good Effects: Peak Effect (Emax) |
1.8; 32.6; 63.0 | <0.0001 sig |
| SECONDARY Good Effects: Time to Maximum (Peak) Effect (TEmax) |
0.7; 2.5; 2.6 | 0.8671 |
| SECONDARY Any Effects: Area Under Effect Curve (AUE) From 0-1 Hour |
0.8; 9.8; 22.6 | <0.0001 sig |
| SECONDARY Any Effects: Area Under Effect Curve (AUE) From 0-2 Hours |
1.8; 26.7; 71.5 | <0.0001 sig |
| SECONDARY Any Effects: Area Under Effect Curve (AUE) From 0-4 Hours |
3.2; 63.8; 172.2 | <0.0001 sig |
| SECONDARY Any Effects: Area Under Effect Curve (AUE) From 0-8 Hours |
6.4; 125.6; 331.8 | <0.0001 sig |
| SECONDARY Any Effects: Area Under Effect Curve (AUE) From 0-12 Hours |
7.8; 155.4; 422.5 | <0.0001 sig |
| SECONDARY Any Effects: Area Under Effect Curve (AUE) From 0-24 Hours |
10.2; 176.4; 510.8 | <0.0001 sig |
| SECONDARY Any Effects: Peak Effect (Emax) |
1.9; 28.7; 62.4 | <0.0001 sig |
| SECONDARY Any Effects: Time to Maximum (Peak) Effect (TEmax) |
0.8; 3.1; 2.8 | 0.3345 |
| SECONDARY Bad Effects: Area Under Effect Curve (AUE) From 0-1 Hour |
0.3; 0.6; 1.5 | 0.0453 sig |
| SECONDARY Bad Effects: Area Under Effect Curve (AUE) From 0-2 Hours |
0.5; 2.6; 7.4 | 0.0041 sig |
| SECONDARY Bad Effects: Area Under Effect Curve (AUE) From 0-4 Hours |
0.9; 7.7; 27.1 | 0.0001 sig |
| SECONDARY Bad Effects: Area Under Effect Curve (AUE) From 0-8 Hours |
1.6; 19.7; 74.6 | <0.0001 sig |
| SECONDARY Bad Effects: Area Under Effect Curve (AUE) From 0-12 Hours |
2.1; 28.4; 110.3 | <0.0001 sig |
| SECONDARY Bad Effects: Area Under Effect Curve (AUE) From 0-24 Hours |
3.6; 36.8; 147.2 | <0.0001 sig |
| SECONDARY Bad Effects: Peak Effect (Emax) |
0.6; 6.6; 20.1 | <0.0001 sig |
| SECONDARY Bad Effects: Time to Maximum (Peak) Effect (TEmax) |
0.9; 2.2; 4.5 | 0.0007 sig |
| SECONDARY Nausea: Area Under Effect Curve (AUE) From 0-1 Hour |
0.4; 0.5; 0.8 | 0.3749 |
| SECONDARY Nausea: Area Under Effect Curve (AUE) From 0-2 Hours |
0.7; 2.1; 3.7 | 0.1211 |
| SECONDARY Nausea: Area Under Effect Curve (AUE) From 0-4 Hours |
1.0; 5.5; 15.3 | 0.0057 sig |
| SECONDARY Nausea: Area Under Effect Curve (AUE) From 0-8 Hours |
1.6; 16.5; 47.1 | 0.0013 sig |
| SECONDARY Nausea: Area Under Effect Curve (AUE) From 0-12 Hours |
2.2; 25.2; 76.9 | 0.0006 sig |
| SECONDARY Nausea: Area Under Effect Curve (AUE) From 0-24 Hours |
3.8; 35.3; 108.3 | 0.0008 sig |
| SECONDARY Nausea: Peak Effect (Emax) |
0.8; 5.2; 14.9 | <0.0001 sig |
| SECONDARY Nausea: Time to Maximum (Peak) Effect (TEmax) |
1.4; 2.5; 4.3 | 0.0806 |
| SECONDARY Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour |
0.3; 0.3; 1.0 | 0.1100 |
| SECONDARY Feel Sick: Area Under Effect Curve (AUE) From 0-2 Hours |
0.6; 1.7; 4.2 | 0.0723 |
| SECONDARY Feel Sick: Area Under Effect Curve (AUE) From 0-4 Hours |
1.0; 5.2; 16.1 | 0.0059 sig |
| SECONDARY Feel Sick: Area Under Effect Curve (AUE) From 0-8 Hours |
1.7; 14.8; 50.7 | 0.0001 sig |
| SECONDARY Feel Sick: Area Under Effect Curve (AUE) From 0-12 Hours |
2.3; 22.5; 80.9 | <0.0001 sig |
| SECONDARY Feel Sick: Area Under Effect Curve (AUE) From 0-24 Hours |
3.9; 31.1; 112.8 | 0.0001 sig |
| SECONDARY Feel Sick: Peak Effect (Emax) |
0.7; 4.9; 16.4 | <0.0001 sig |
| SECONDARY Feel Sick: Time to Maximum (Peak) Effect (TEmax) |
0.9; 1.8; 4.3 | 0.0007 sig |
| SECONDARY Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour |
0.4; 2.4; 3.6 | 0.2117 |
| SECONDARY Sleepy: Area Under Effect Curve (AUE) From 0-2 Hours |
0.7; 9.1; 21.3 | 0.0002 sig |
| SECONDARY Sleepy: Area Under Effect Curve (AUE) From 0-4 Hours |
1.7; 35.9; 74.2 | <0.0001 sig |
| SECONDARY Sleepy: Area Under Effect Curve (AUE) From 0-8 Hours |
4.2; 97.6; 199.2 | <0.0001 sig |
| SECONDARY Sleepy: Area Under Effect Curve (AUE) From 0-12 Hours |
5.3; 138.5; 287.5 | <0.0001 sig |
| SECONDARY Sleepy: Area Under Effect Curve (AUE) From 0-24 Hours |
7.6; 175.5; 378.7 | <0.0001 sig |
| SECONDARY Sleepy: Peak Effect (Emax) |
1.5; 27.1; 43.9 | <0.0001 sig |
| SECONDARY Sleepy: Time to Maximum (Peak) Effect (TEmax) |
1.1; 4.0; 5.3 | 0.0253 sig |
| SECONDARY Dizzy: Area Under Effect Curve (AUE) From 0-1 Hour |
0.4; 0.9; 3.0 | 0.0062 sig |
| SECONDARY Dizzy: Area Under Effect Curve (AUE) From 0-2 Hours |
0.6; 2.8; 9.9 | 0.0009 sig |
| SECONDARY Dizzy: Area Under Effect Curve (AUE) From 0-4 Hours |
1.0; 9.5; 26.1 | 0.0042 sig |
| SECONDARY Dizzy: Area Under Effect Curve (AUE) From 0-8 Hours |
1.7; 20.9; 56.7 | 0.0039 sig |
| SECONDARY Dizzy: Area Under Effect Curve (AUE) From 0-12 Hours |
2.4; 27.4; 71.4 | 0.0051 sig |
| SECONDARY Dizzy: Area Under Effect Curve (AUE) From 0-24 Hours |
4.0; 36.0; 85.5 | 0.0083 sig |
| SECONDARY Dizzy: Peak Effect (Emax) |
0.7; 5.5; 13.7 | 0.0018 sig |
| SECONDARY Dizzy: Time to Maximum (Peak) Effect (TEmax) |
0.5; 2.0; 2.4 | 0.3986 |
| SECONDARY Overall Drug Liking Effect at 24 Hours |
50.6; 58.8; 69.8 | 0.0029 sig |
| SECONDARY Take Drug Again Effect at 24 Hours |
49.8; 58.0; 70.6 | 0.0050 sig |
| SECONDARY Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour |
0.0; -0.5; -1.2 | <0.0001 sig |
| SECONDARY Pupillometry: Area Under Effect Curve (AUE) From 0-2 Hours |
0.0; -1.7; -4.1 | <0.0001 sig |
| SECONDARY Pupillometry: Area Under Effect Curve (AUE) From 0-4 Hours |
-0.1; -5.4; -10.3 | <0.0001 sig |
| SECONDARY Pupillometry: Area Under Effect Curve (AUE) From 0-8 Hours |
0.0; -13.8; -22.5 | <0.0001 sig |
| SECONDARY Pupillometry: Area Under Effect Curve (AUE) From 0-12 Hours |
0.7; -20.8; -32.6 | <0.0001 sig |
| SECONDARY Pupillometry: Area Under Effect Curve (AUE) From 0-24 Hours |
3.5; -34.2; -51.8 | <0.0001 sig |
| SECONDARY Pupillometry: Peak Effect (Emax) |
5.6; 3.9; 2.8 | <0.0001 sig |
| SECONDARY Pupillometry: Time to Maximum (Peak) Effect (TEmax) |
4.8; 5.6; 3.2 | 0.0262 sig |
| SECONDARY Time to Reach Maximum Observed Plasma Concentration (Tmax) of Morphine |
0.9; 0.7 | 0.0181 sig |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) of Morphine |
79308.6; 103621 | <0.0001 sig |
| SECONDARY Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-1)] of Morphine |
52644.9; 67920.1 | 0.0004 sig |
| SECONDARY Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-2)] of Morphine |
112989; 129721 | 0.0065 sig |
| SECONDARY Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-4)] of Morphine |
197745; 199442 | 0.6399 |
| SECONDARY Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-8)] of Morphine |
269743; 263270 | 0.9057 |
| SECONDARY Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-12)] of Morphine |
303428; 288324 | 0.4250 |
| SECONDARY Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)] of Morphine |
376260; 335357 | 0.0204 sig |
| SECONDARY Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Morphine |
551755; 369270 | 0.0005 sig |
| SECONDARY Time to Reach Maximum Observed Plasma Concentration (Tmax) of Naltrexone |
0.8 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) of Naltrexone |
978.83 | — |
| SECONDARY Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-1)] of Naltrexone |
619.24 | — |
| SECONDARY Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-2)] of Naltrexone |
1270.91 | — |
| SECONDARY Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-4)] of Naltrexone |
2018.23 | — |
| SECONDARY Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-8)] of Naltrexone |
2577.19 | — |
| SECONDARY Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-12)] of Naltrexone |
2813.34 | — |
| SECONDARY Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)] of Naltrexone |
3159.91 | — |
| SECONDARY Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Naltrexone |
3320.90 | — |
| SECONDARY Time to Reach Maximum Observed Plasma Concentration (Tmax) of Naltrexone Metabolite (6-beta-naltrexol) |
1.0 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) of Naltrexone Metabolite (6-beta-naltrexol) |
6226.3 | — |
| SECONDARY Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-1)] of Naltrexone Metabolite (6-beta-naltrexol) |
3934.5 | — |
| SECONDARY Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-2)] of Naltrexone Metabolite (6-beta-naltrexol) |
8916.1 | — |
| SECONDARY Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-4)] of Naltrexone Metabolite (6-beta-naltrexol) |
16532.5 | — |
| SECONDARY Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-8)] of Naltrexone Metabolite (6-beta-naltrexol) |
26634.5 | — |
| SECONDARY Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-12)] of Naltrexone Metabolite (6-beta-naltrexol) |
33324.9 | — |
| SECONDARY Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)] of Naltrexone Metabolite (6-beta-naltrexol) |
47809.1 | — |
| SECONDARY Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Naltrexone Metabolite (6-beta-naltrexol) |
74931.5 | — |
Summary
The primary purpose of this study is to determine the abuse potential of EMBEDA compared to controlled release morphine when crushed and taken orally by non-dependent recreational opioid users; secondary purposes include to determine the abuse potential of crushed EMBEDA relative to placebo and and to compare the pharmacokinetics and safety of crushed EMBEDA with crushed controlled-release morphine and crushed placebo.
Eligibility Criteria
Inclusion Criteria
- Subject is a recreational opioid user who is NOT physically dependent on opioids based on Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition-Text Revision (DSM-IV-TR) criteria, and the Naloxone Challenge. A recreational opioid user is defined as recreationally abusing opioids for non-therapeutic purposes (i.e., for psychoactive effects) on at least 10 occasions within the last year and at least once in the 12 weeks prior to Visit 1.
- Subject is in generally good health as determined by medical history, physical examination, vital signs, clinical laboratory tests, and 12-lead electrocardiogram (ECG).
Exclusion Criteria
- Has a history or current diagnosis of substance dependence (excluding caffeine and nicotine), as assessed by the Investigator using the DSM IV-TR criteria.
- Has participated in, is currently participating in, or is seeking treatment for substance- and/or alcohol-related disorders (excluding nicotine and caffeine).
- History or presence of any clinically significant illness (e.g., cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, oncologic, musculoskeletal, or psychiatric) or any other condition, which in the opinion of the Investigator would jeopardize the safety of the subject or the validity of the study results.
- Has a known allergy or history of hypersensitivity to morphine sulfate, opioids in general, naltrexone hydrochloride (HCl) or similar compounds and/or the known excipients in the investigational drug products.
- Has any condition in which an opioid is contraindicated (e.g., significant respiratory depression, acute or severe bronchial asthma or hypercarbia, or is suspected of having paralytic ileus).
- Females who are pregnant, lactating, or are planning to become pregnant during the course of the study. Females with a positive serum pregnancy test at Visit 1 or at any subsequent study visit will be excluded from participating in the study.
Data sourced from ClinicalTrials.gov (NCT01380093). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.