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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01309841




Registration number
NCT01309841
Ethics application status
Date submitted
4/03/2011
Date registered
7/03/2011
Date last updated
1/06/2015

Titles & IDs
Public title
Assessment of Efficacy and Safety in Patients With Non-cancer-related Pain and Opioid-induced Constipation
Scientific title
A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of NKTR-118 in Patients With Non-Cancer-Related Pain and Opioid-Induced Constipation (OIC)
Secondary ID [1] 0 0
2011-001987-24
Secondary ID [2] 0 0
D3820C00004
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Opioid-Induced Constipation (OIC) 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - NKTR-118
Treatment: Drugs - NKTR-118
Treatment: Drugs - Placebo

Experimental: 1 - Oral treatment

Experimental: 2 - Oral treatment

Placebo Comparator: 3 - Oral treatment


Treatment: Drugs: NKTR-118
12.5 mg oral tablet once daily

Treatment: Drugs: NKTR-118
25 mg oral tablet once daily

Treatment: Drugs: Placebo
Oral tablet once daily

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Response (Responder/Non-responder) to Study Drug During Weeks 1 to 12 - Responder was defined as having at least 3 spontaneous bowel movements (SBMs)/week with at least 1 SBM/week increase over baseline for at least 9 out of the 12 treatment weeks and 3 out of the last 4 treatment weeks during the double-blind treatment period. An SBM is a bowel movement occurring 24 hours or more since the last use of rescue medication.
Timepoint [1] 0 0
Baseline (Week 1) to end of treatment (Week 12)
Secondary outcome [1] 0 0
Response (Responder/Non-responder) to Study Drug in the LIR Subgroup During Weeks 1 to 12 - Responder is defined as having at least 3 SBMs/week, with at least 1 SBM/week increase over baseline for at least 9 out of 12 weeks and at least 3 out of the last 4 weeks.
Timepoint [1] 0 0
Baseline (Week 1) to end of treatment (Week 12)
Secondary outcome [2] 0 0
Time (in Hours) to First Post-dose Laxation Without the Use of Rescue Laxatives Within the Previous 24 Hours
Timepoint [2] 0 0
12 weeks
Secondary outcome [3] 0 0
Change From Baseline in Mean Number of Days Per Week With at Least 1 SBM During Weeks 1 to 12
Timepoint [3] 0 0
12 weeks
Secondary outcome [4] 0 0
Change From Baseline in Degree of Straining - A single-item straining question was asked via the eDiary: "How much did you strain during your bowel movement?" Patients responded on a 5 point Likert scale: 1=Not at all; 2=A little bit; 3=A moderate amount; 4=A great deal; 5=An extreme amount. A negative change from baseline indicates improvement.
Timepoint [4] 0 0
Baseline (Week 1) to end of treatment (Week 12)
Secondary outcome [5] 0 0
Change From Baseline in Stool Consistency (Bristol Stool Scale) - Patients rated stool consistency through completion of the BSS after each BM. The 7 stool types are: 1. Separate hard lumps, like nuts (hard to pass); 2. Sausage-shaped, but lumpy; 3. Like sausage, but with cracks on its surface; 4. Like a sausage or snake, smooth and soft; 5. Soft blobs with clear cut edges (passed easily); 6. Fluffy pieces with ragged edges, a mushy stool; 7. Watery, no solid pieces. A positive change from baseline indicates improvement.
Timepoint [5] 0 0
Baseline (Week 1) to end of treatment (Week 12)
Secondary outcome [6] 0 0
Change From Baseline in Percent Numbers of Days With a CSBM (Complete Spontaneous Bowel Movement) - A single-item question on the completeness of evacuation, developed and validated through 1:1 interviews with OIC patients, was asked via the eDiary: "Did you feel like your bowels were completely empty after the bowel movement?" Patients provided a yes or a no response. A positive change from baseline indicates improvement.
Timepoint [6] 0 0
Baseline (Week 1) to end of treatment (Week 12)
Secondary outcome [7] 0 0
Change From Baseline in Mean Spontaneous Bowel Movements/Week - The number of spontaneous bowel movements/week was determined from the patient's eDiary.
Timepoint [7] 0 0
Baseline (Week 1) to end of treatment (Week 12)
Secondary outcome [8] 0 0
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 to first post-dose laxation without the use of rescue laxatives within the last 24 hours was calculated in hours as: Date/Time of first post-dose laxation without rescue - First dose date/time.
Timepoint [8] 0 0
Baseline (Week 1) to end of treatment (Week 12)
Secondary outcome [9] 0 0
Change From Baseline in Patient Assessment of Constipation Symptoms Questionnaire (PAC-SYM) - The PAC-SYM questionnaire is a 12-item questionnaire that evaluates the severity of symptoms of constipation in 3 domains (stool, rectal, and abdominal symptoms) on a 5-point Likert scale ranging from 0 (absent) to 4 (very severe) in the 2 weeks (14 days) prior to assessment. Each domain score is the mean of the non-missing items for that domain. The total score is the mean of all non-missing items (ie, symptoms). The range of the domain or total score is 0 (response is 'absent' for each item) to 4 (response is 'very severe' for each item). A negative change from baseline indicates improvement.
Timepoint [9] 0 0
Baseline (Week 1) to end of treatment (Week 12)
Secondary outcome [10] 0 0
Change From Baseline in Patient Assessment of Constipation Quality of Life (PAC-QOL) Satisfaction Domain - The PAC-QOL scale is a 28-item self-report instrument designed to evaluate the burden of constipation on patients' everyday functioning and well-being in the 2 weeks (14 days) prior to assessment. Each item is rated on a 5-point Likert scale ranging from 0 (not at all) to 4 (extremely). The instrument can be used to generate an overall score, but is also reported to assess 4 specific constipation-related domains including: 1) Worries and concerns (11 items), 2) Physical discomfort (4 items), 3) Psychosocial discomfort (8 items), and 4) Satisfaction (5 items). Each domain score is the mean of the non-missing items for that domain. The total score is the mean of all non-missing items. The range of the domain or total score is 0 (response is 'not at all' for each item) to 4 (response is 'extremely' for each item). A negative change from baseline indicates improvement.
Timepoint [10] 0 0
Baseline (Week 1) to end of treatment (Week 12)

Eligibility
Key inclusion criteria
- Provision of written informed consent prior to any study-specific procedures.

- Men and women who are between the ages of =18 and <85 years.

- Self-reported active symptoms of OIC at screening (<3 SBMs/week and experiencing =1
reported symptom of hard/lumpy stools, straining, or sensation of incomplete
evacuation/anorectal obstruction in at least 25% of BMs over the previous 4 weeks);
and Documented confirmed OIC (<3 SBMs/week on average over the 2-week OIC confirmation
period.

- Receiving a stable maintenance opioid regimen consisting of a total daily dose of 30
mg to 1000 mg of oral morphine, or equianalgesic amount(s) of 1 or more other opioid
therapies for a minimum of 4 weeks prior to screening for non-cancer-related pain with
no anticipated change in opioid dose requirement over the proposed study period as a
result of disease progression.

- Willingness to stop all laxatives and other bowel regimens including prune juice and
herbal products throughout the 2-week OIC confirmation period and the 12-week
treatment period, and to use only bisacodyl as rescue medication if a BM has not
occurred within at least 72 hours of the last recorded BM.
Minimum age
18 Years
Maximum age
84 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Patients receiving Opioid regimen for treatment of pain related to cancer.

- History of cancer within 5 years from first study visit 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,WA
Recruitment hospital [1] 0 0
Research Site - Broadmeadow
Recruitment hospital [2] 0 0
Research Site - Darlinghurst
Recruitment hospital [3] 0 0
Research Site - Port Kembla
Recruitment hospital [4] 0 0
Research Site - Westmead
Recruitment hospital [5] 0 0
Research Site - Greenslopes
Recruitment hospital [6] 0 0
Research Site - Adelaide
Recruitment hospital [7] 0 0
Research Site - Fremantle
Recruitment hospital [8] 0 0
Research Site - Nedlands
Recruitment postcode(s) [1] 0 0
- Broadmeadow
Recruitment postcode(s) [2] 0 0
- Darlinghurst
Recruitment postcode(s) [3] 0 0
- Port Kembla
Recruitment postcode(s) [4] 0 0
- Westmead
Recruitment postcode(s) [5] 0 0
- Greenslopes
Recruitment postcode(s) [6] 0 0
- Adelaide
Recruitment postcode(s) [7] 0 0
- Fremantle
Recruitment postcode(s) [8] 0 0
- Nedlands
Recruitment outside Australia
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Banska Bystrica
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Bratislava
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Kosice
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Presov

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
AstraZeneca
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to evaluate the effect and safety of NKTR-118 treatment of
opioid-induced constipation in patients with non-cancer-related pain, including those
patients that have inadequate response to laxative therapy (LIR).
Trial website
https://clinicaltrials.gov/show/NCT01309841
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Mark Sostek
Address 0 0
AstraZeneca Pharmaceuticals, Wilm DE
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications