E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Opioid-induced constipation in subjects with non-malignant pain Tratamiento del estreñimiento inducido por opiáceos en sujetos con dolor de origen no maligno |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10010774 |
E.1.2 | Term | Constipation |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary: To evaluate the safety, efficacy, and tolerability of subcutaneous MOA-728 versus placebo in subjects with nonmalignant pain who have opioid-induced constipation. |
|
E.2.2 | Secondary objectives of the trial |
Secondary: To explore subject-reported outcomes for benefits of treatment with MOA-728. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male and female subjects aged 18 years or older. 2. Subjects weighing ? 40 kg. 3. A history of pain with documentation of a nonmalignant condition underlying the pain of at least 2 month?s duration before the screening visit. 4. Taking oral, transdermal, intravenous, or SC opioids for at least 1 month and receiving a daily dose ? 50 mg of oral morphine equivalents per day for at least 2 weeks before the screening visit with no anticipated changes during the study. 5. A history of constipation due to opioid use for at least 1 month before the screening visit. Constipation is defined as < 3 rescue-free (no laxative use during the prior 24 hours) bowel movements (RFBMs) per week on average and 1 or more of the following: i) Hard or lumpy stools. ii) Straining during bowel movements. iii) A sensation of incomplete evacuation after bowel movements. 6. All female and male subjects who are biologically capable of having children must agree and commit to the use of a reliable method of birth control for the duration of the study and for 15 days after the last dose of test article administration. A subject is biologically capable of having children even if he or she is using contraceptives or if his or her sexual partner is sterile or using contraceptives. 7. Willingness to discontinue all prestudy laxative therapy and use only the study-permitted rescue laxative during the screening, treatment, and follow-up periods. 8. Willingness and ability to participate in all aspects of the study, including use of subcutaneous medication (administered by self or designee), completion of subject evaluations, attending scheduled clinic visits, access to a telephone, and compliance with all protocol requirements as evidenced by written informed consent. 9. Ambulatory, capable of all self-care, and up and about more than 50% of waking hours. |
|
E.4 | Principal exclusion criteria |
1. Prior treatment with SC methylnaltrexone. 2. Pregnant or breastfeeding women. 3. A diagnosis of bowel obstruction, fecal incontinence, rectal prolapse, acute diverticulitis, or other significant GI disorders. 4. Any history of any inflammatory bowel disease or toxic megacolon or a history of irritable bowel syndrome within 6 months before the screening visit. 5. A recent history of rectal bleeding unexplained by hemorrhoids or fissures. 6. Need for manual disimpaction or pelvic floor support techniques, including manual maneuvers, within 14 days before the screening visit. 7. Clinical evidence of outlet obstruction or impaction. If suspected, a rectal examination must be performed to rule out obstruction or impaction. 8. A history of malignancy, other than basal- or squamous-cell skin carcinoma, within 5 years before the screening visit. 9. A history of laxative use due to chronic constipation before the initiation of opioid therapy. 10. A history of alcohol or drug abuse within 1 year before the screening visit. 11. Any major illness/condition or unstable hepatic, renal, pulmonary, cardiovascular (including uncontrolled hypertension), ophthalmologic, neurologic, psychiatric, or any other medical condition that, in the investigator?s judgment, will substantially increase the risk associated with the subject?s participation in and completion of, the study, or could preclude the evaluation of the subject?s response. 12. A history or presence of symptomatic orthostatic hypotension. 13. Other clinically important abnormalities on screening physical examination findings, laboratory test results, or electrocardiogram (ECG) findings. 14. A calculated creatinine clearance (Cockcroft-Gault glomerular filtration rate [GFR]) < 30 mL/min. 15. Planned surgery during the study. 16. Known or suspected allergy to opioids, opioid derivatives, or opioid antagonists (eg, codeine, naltrexone, or naloxone) or other compounds related to these classes of medications. 17. Current treatment with partial opioid agonists (eg, buprenorphine) or combination agonists/antagonists. 18. Urine drug screen negative for the presence of opioids. 19. Urine drug screen positive for a substance of abuse that is not explained by a prescribed medication reported by the subject. 20. Patients who received opioid maintenance therapy (eg, methadone, buprenorphine) for the treatment of addiction. 21. Involvement in litigation related to the subject?s underlying medical condition. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Two coprimary efficacy endpoints are: 1. the proportion of subjects having a RFBM within 4 hours of the first dose administration, and 2. the percentage of injections resulting in any RFBM within 4 hours during the double-blind period. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 35 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
Last visit of the last subject. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |