E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Opioid-induced constipation (OIC) |
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E.1.1.1 | Medical condition in easily understood language |
Constipation after taking opioid drugs |
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E.1.1.2 | Therapeutic area | Body processes [G] - Digestive System and Oral Physiological Phenomena [G10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10010774 |
E.1.2 | Term | Constipation |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
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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 |
The primary objective of this study is to compare the efficacy of NKTR-118 12.5 and 25 mg with placebo regarding long-term safety and tolerability in the treatment of patients who have OIC. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective of this study is to assess the impact of NKTR-118 12.5 and 25mg on symptoms of constipation and quality of life. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Must have completed the 12-week study D3820C00004 through Visit 8. Provision of written informed consent prior to any study-specific procedures. Men and women who were between the ages of ≥18 and < 85 years at the time of the screening visit for study D3820C00004. Continuing to receive a stable maintenance opioid regimen consisting of a total daily dose of 30 mg ot 1000 mg of oral morphine, or equianalgesic amount(s) of 1 or more other opioid therapies. Willingness to continue abstinence from all laxatives and other bowel regimens including prune juice and herbal products throughout this additional 12-week treatment period, and to use only bisacodyl as rescue medication if a bowel movement (BM) has not occurred within at least 72 hours of the last recoreded BM. |
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E.4 | Principal exclusion criteria |
Patients receiving Opioid regimen for treatment of pain related to cancer. History of cancer within 5 years from screening visit of study D3820C00004 with the exception of basal cell cancer and squamous cell skin cancer. Medical conditions and treatments associated with diarrhea, intermittent loose stools, or constipation. Other issues to the gastrointestinal tract that could impose a risk to the patient. Pregnancy or lactation. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1) Incidence, nature and intensty of adverse events (AEs), treatment-related AEs, serious adverse events (SAEs), AEs leading to discontinuation, and specific safety areas of interest. Changes in vital signs and physical examination.
2) Change from baseline in mean daily prescribed opioid dose.
3) Mean bisacody dose per week.
4) Change from baseline in Numeric Rating Scale (NRS) pain score.
5) Observed and change from baseline in composite score of Himmelsbach scale.
6) Changes in laboratory assessments (ie chemistry, hematology and urinalysis) and electrocardiograms (ECGs)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1)AEs will be collected from first dose to last visit (14 weeks). Vital signs will be collected and performed throughout the (14 weeks), at all 5 visits. Physical examinations will be performed at beginning and end of the study period (14 weeks).
2)Will be collected throughout the (14 weeks) at Visits 1,2,3,4, and 5.
3)Will be assessed for the following time intervals: between Enrollment (V1) to Week 4 (V2) and Week 4 (V2) to Week 12 (V4).
4)Will be calculated at Weeks 4 (V2), 8 (V3) and 12 (V4).
5)Will be collected at Enrollment (V1) and Week 12 (V4).
6)Laboratory assessments and ECGs will be collected at Enrollment (V1), Week 12 (V4) and Follow-up (V5). Urinalysis will be performed at Enrollment (V1) and Week 12 (V4).
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E.5.2 | Secondary end point(s) |
1) Change from baseline in Patient Assessment of Constipation Symptoms (PAC-SYM)
2) Change from baseline in Patient Assessment of Constipation Quality of Life (PAC-QOL) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) Will be collected at Enrollment (Visit 1), Week 4 (Visit 2), Week 12 (Visit 4) and Follow-up (Visit 5).
2) Will be collected at Enrollment (Visit 1), Week 4 (Visit 2), Week 12 (Visit 4) and Follow-up (Visit 5).
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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 | Yes |
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 | Yes |
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 | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
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.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 17 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 23 |
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 | No |
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 |
Australia |
Germany |
Slovakia |
United States |
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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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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 | 4 |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |