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 |
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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 |
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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: The primary objective of the study is to evaluate the long-term safety and tolerability of the subcutaneous formulation of MOA-728 in subjects with opioid-induced constipation who have nonmalignant pain. |
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E.2.2 | Secondary objectives of the trial |
Secondary: The secondary objective of the study is to assess the long-term efficacy of the subcutaneous formulation of MOA-728 in subjects with opioid-induced constipation who have nonmalignant pain. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female subjects aged 18 years or older. 2. A history of pain of at least 2 months? duration before the screening visit due to a documented underlying nonmalignant condition. 3. Stable medical status for at least 1 month before the screening visit. 4. Taking oral, transdermal, intravenous, or subcutaneous opioids daily for at least 1 month, with anticipated continuing daily opioid therapy for the duration of the study. 5. A history of constipation due to opioid use during the 1 month before the screening visit. Subjects must satisfy 2 or more of the following criteria during the month prior to the screening visit to be eligible: a. Hard or lumpy stools for at least 25% of the bowel movements. b. Straining during at least 25% of the bowel movements. c. A sensation of incomplete evacuation after at least 25% of the bowel movements. d. Use of manual maneuvers (eg, digital evacuation, support of pelvic floor) to facilitate bowel movements at least 25% of the time. e. Fewer than 3 bowel movements per week. 6. At least 1 bowel movement in the week prior to the screening visit. 7. 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. A subject is biologically capable of having children if he or she is using contraceptives or if his or her sexual partner is sterile or using contraceptives. 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, 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. |
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E.4 | Principal exclusion criteria |
1. Received any investigational drugs or devices other than MOA-728 within 4 weeks before administration of the first dose of test article. 2. Pregnant, breastfeeding, or plans to become pregnant during the study. 3. A diagnosis of bowel obstruction, fecal incontinence, rectal prolapse, or other significant GI disorders. 4. A history of active inflammatory bowel disease, irritable bowel syndrome, or megacolon within 6 months before the screening visit. 5. A history of rectal bleeding unexplained by hemorrhoids or fissures. 6. Clinical evidence of outlet obstruction or impaction. 7. A history of malignancy, other than basal cell or squamous cell skin carcinoma, within 5 years before the screening visit. 8. A history of chronic constipation before the initiation of opioid therapy. 9. A history of alcohol or drug abuse within 1 year before the screening visit. 10. Any unstable hepatic, renal, pulmonary, cardiovascular (including uncontrolled hypertension), ophthalmologic, neurologic, psychiatric, or any other medical condition that might compromise the study or put the subject at greater risk during study participation. 11. A history or presence of symptomatic orthostatic hypotension. 12. Other clinically important abnormalities on the screening physical examination, electrocardiogram (ECG), or laboratory tests. 13. A calculated creatinine clearance (Cockcroft-Gault glomerular filtration rate [GFR]) <30 mL/min. 14. Urine drug screen positive for a substance of abuse that is not explained by a prescribed medication reported by the subject. 15. Planned surgery during the study. 16. Known or suspected allergy or other contraindication to opioids, opioid derivatives, or opioid antagonists (eg, codeine, naltrexone, or naloxone). 17. Current treatment with partial opioid agonists (eg, buprenorphine) or combination agonists/antagonists. 18. Involvement in current litigation related to the subject's underlying medical condition. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety and tolerability will be evaluated by collection of adverse events, laboratory assessments, physical examinations, vital signs measurements, electrocardiograms, Pain Intensity Scale, and the opioid withdrawal scales. |
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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 | No |
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 | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
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 |
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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
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Last visit of the last subject. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |