Assessment of Efficacy and Safety in Patients With Non-cancer-related Pain and Opioid-induced Constipation

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01309841
First received: March 4, 2011
Last updated: May 29, 2015
Last verified: May 2015
Results First Received: October 13, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Opioid-Induced Constipation (OIC)
Interventions: Drug: NKTR-118
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This multicenter study was conducted in Australia, Germany, Slovakia, and the United States between 14 March 2011 and 16 August 2012.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The study duration was up to 18 weeks, consisting of an initial screening period lasting up to 2 weeks, a 2-week OIC confirmation period, during which the diagnosis of OIC and stability of the opioid regimen were confirmed, a 12-week treatment period, and a follow-up visit 2 weeks after the last dose of study drug.

Reporting Groups
  Description
NKTR-118 12.5 mg NKTR-118 12.5 QD, oral treatment
NKTR-118 25 mg NKTR-118 25 mg QD, oral treatment
Placebo Placebo QD, oral treatment

Participant Flow:   Overall Study
    NKTR-118 12.5 mg     NKTR-118 25 mg     Placebo  
STARTED     217     218     217  
COMPLETED     178     177     180  
NOT COMPLETED     39     41     37  
Other                 0                 1                 1  
Lost to Follow-up                 7                 6                 4  
Study-Specific Withdrawal Criteria                 3                 1                 2  
Lack of Efficacy                 0                 0                 2  
Adverse Event                 9                 22                 11  
Death                 1                 0                 0  
Eligibility Criteria Not Fulfilled                 0                 0                 1  
Withdrawal by Subject                 17                 6                 13  
Did Not Receive Treatment                 2                 0                 1  
Severe non-compliance with protocol                 0                 5                 2  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
A total of 11 patients (4 patients each in the NKTR-118 25 mg and 12.5 mg groups and 3 patients in the placebo group) had been previously randomized within the NKTR-118 program at a different study center. These patients were excluded from the ITT and Safety analysis sets. Baseline characteristics are summarized based on the ITT analysis set.

Reporting Groups
  Description
NKTR-118 12.5 mg NKTR-118 12.5 QD, oral treatment
NKTR-118 25 mg NKTR-118 25 mg QD, oral treatment
Placebo Placebo QD, oral treatment
Total Total of all reporting groups

Baseline Measures
    NKTR-118 12.5 mg     NKTR-118 25 mg     Placebo     Total  
Number of Participants  
[units: participants]
  213     214     214     641  
Age  
[units: Years]
Mean (Standard Deviation)
  51.9  (10.43)     52.2  (10.29)     52.9  (9.99)     52.3  (10.23)  
Gender  
[units: Participants]
       
Female     135     118     140     393  
Male     78     96     74     248  
Race/Ethnicity, Customized  
[units: Participants]
       
American Indian or Alaska Native     1     0     2     3  
Asian     5     1     4     10  
Native Hawaiian or Other Pacific Islander     0     0     0     0  
Black or African American     42     38     44     124  
White     164     173     160     497  
Other     1     2     4     7  
Baseline laxative response status [1]
[units: Participants]
       
Laxative Inadequate Response (LIR)     115     117     118     350  
Laxative Adequate Response (LAR)     3     2     2     7  
Laxative Unknown Response (LUR)     95     95     94     284  
[1] Laxative response status was determined at the screening visit (Visit 1) based on the Baseline Laxative Response Status Questionnaire. Patients were classified as: Laxative Inadequate Responder (LIR: patients who reported moderate, severe, or very severe symptoms in at least 1 of the 4 stool symptom domains); Laxative Adequate Responder (LAR: patients who reported no symptoms or only mild symptoms); and Laxative Unknown Responder (LUR: patients who had not taken laxatives over the previous 2 weeks or who had taken 1 or more laxative classes on <4 days over the previous 2 weeks).



  Outcome Measures
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1.  Primary:   Response (Responder/Non-responder) to Study Drug During Weeks 1 to 12   [ Time Frame: Baseline (Week 1) to end of treatment (Week 12) ]

2.  Secondary:   Response (Responder/Non-responder) to Study Drug in the LIR Subgroup During Weeks 1 to 12   [ Time Frame: Baseline (Week 1) to end of treatment (Week 12) ]

3.  Secondary:   Time (in Hours) to First Post-dose Laxation Without the Use of Rescue Laxatives Within the Previous 24 Hours   [ Time Frame: 12 weeks ]

4.  Secondary:   Change From Baseline in Mean Number of Days Per Week With at Least 1 SBM During Weeks 1 to 12   [ Time Frame: 12 weeks ]

5.  Secondary:   Change From Baseline in Degree of Straining   [ Time Frame: Baseline (Week 1) to end of treatment (Week 12) ]

6.  Secondary:   Change From Baseline in Stool Consistency (Bristol Stool Scale)   [ Time Frame: Baseline (Week 1) to end of treatment (Week 12) ]

7.  Secondary:   Change From Baseline in Percent Numbers of Days With a CSBM (Complete Spontaneous Bowel Movement)   [ Time Frame: Baseline (Week 1) to end of treatment (Week 12) ]

8.  Secondary:   Change From Baseline in Mean Spontaneous Bowel Movements/Week   [ Time Frame: Baseline (Week 1) to end of treatment (Week 12) ]

9.  Secondary:   Time (in Hours) to First Post-dose Laxation Without the Use of Rescue Laxatives Within the Previous 24 Hours in the Laxative Inadequate Response (LIR) Subgroup   [ Time Frame: Baseline (Week 1) to end of treatment (Week 12) ]

10.  Secondary:   Change From Baseline in Patient Assessment of Constipation Symptoms Questionnaire (PAC-SYM)   [ Time Frame: Baseline (Week 1) to end of treatment (Week 12) ]

11.  Secondary:   Change From Baseline in Patient Assessment of Constipation Quality of Life (PAC-QOL) Satisfaction Domain   [ Time Frame: Baseline (Week 1) to end of treatment (Week 12) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Mark Sostek
Organization: AstraZeneca
e-mail: ClinicalTrialTransparency@astrazeneca.com


No publications provided by AstraZeneca

Publications automatically indexed to this study:

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01309841     History of Changes
Other Study ID Numbers: D3820C00004, 2011-001987-24
Study First Received: March 4, 2011
Results First Received: October 13, 2014
Last Updated: May 29, 2015
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
Germany: Federal Institute for Drugs and Medical Devices
Slovakia: State Institute for Drug Control
United States: Food and Drug Administration