Opioid Induced Constipation (OIC)
Conditions
Keywords
NKTR, constipation, opioid, induced, bowel, dysfunction, Naloxol, Naloxone, Narcan, PEG naloxol, OIC, OBD, Nektar
Brief summary
Study (07-IN-NX003) is a Phase 2, multi-center, placebo-controlled, double-blind, randomized, dose-escalation trial. It is designed to investigate the safety, efficacy and tolerability of NKTR-118 (PEG-naloxol) in patients with opioid-induced constipation (OIC) and other clinical manifestations of opioid-induced bowel dysfunction (OBD). The objective of this study is to evaluate the safety, effectiveness and pharmacokinetics of NKTR-118 at 4 different doses.
Interventions
DRUGNKTR-118
5 mg, 25 mg, 50 mg or 100 mg, oral,once daily (QD)
DRUGplacebo
placebo, oral, once daily (QD)
Sponsors
Nektar Therapeutics
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: * 18 years of age or older, male or female * Receiving a stable opioid regimen * Documented opioid-induced constipation * Willingness to stop all laxatives and other bowel regimens. The use of constipation rescue medication will be allowed during the study. Main
Exclusion criteria
* Life expectancy less than 6 months * Active substance abuse * Fecal incontinence, irritable bowel syndrome, inflammatory bowel disease, or other active medical disorders associated with diarrhea or intermittent loose stools or constipation * Pregnant or breast-feeding * Any receipt of an investigational medication within 30 days of screening * History or presence of specific cardiac, neurologic, endocrine and/or psychiatric conditions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Spontaneous Bowel Movements (SBMs) Per Week During Week 1 | Days 1 through 7 | Change from baseline in SBMs/week during Week 1 was defined as SBMs/week during the first week of double-blind study medication (between Visit 4 and Visit 6) minus baseline SBMs/week. Baseline was defined as the average SBMs/week during the 2-week OIC screening period. An SBM was defined as a BM without the use of laxatives in the previous 24 hours as recorded in the e-diary. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in SBMs/Week Across the 28-day Double-blind Period | Days 1 through 28 | Change from baseline in SBMs/week across the 28-day double-blind period was calculated as SBMs/week during 28-day double-blind study treatment period minus baseline SBMs/week. Baseline was defined as the average SBMs/week during the 2-week OIC screening period. |
| Change From Baseline in Patient Assessment of Constipation-Quality of Life (PAC-QOL) Questionnaire | Days 1 through 28 | 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 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. |
| Change From Baseline in Patient Assessment of Constipation-Symptoms (PAC-SYM) Questionnaire | Days 1 through 28 | 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 is 0 (response is 'absent' for each item) to 4 (response is 'very severe' for each item). A negative change from baseline indicates improvement. |
Countries
United States
Participant flow
Recruitment details
This multicenter study was conducted in Canada, Germany, Romania, and the United States between 04 January 2008 and 23 March 2009.
Pre-assignment details
The study duration was up to 11 weeks, consisting of an initial screening period lasting up to 10 days, a 14-day OIC confirmation period, during which the OIC diagnosis was confirmed, a 7-day single-blind placebo run-in period, a 29-day double-blind treatment period, and a follow-up visit 2 weeks after the last dose of study drug.
Participants by arm
| Arm | Count |
|---|---|
| Placebo 5 mg Placebo for NKTR-118 5 mg QD, oral treatment | 31 |
| NKTR-118 5 mg NKTR-118 5 mg QD, oral treatment | 31 |
| Placebo 25 mg Placebo for NKTR-118 25 mg QD, oral treatment | 27 |
| NKTR-118 25 mg NKTR-118 25 mg QD, oral treatment | 29 |
| Placebo 50 mg Placebo for NKTR-118 50 mg QD, oral treatment | 37 |
| NKTR-118 50 mg NKTR-118 50 mg QD, oral treatment | 30 |
| Total | 185 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Double-blind Treatment Period | Adverse Event | 1 | 1 | 0 | 1 | 2 | 10 |
| Double-blind Treatment Period | Inclusion/Exclusion Criteria Not Met | 0 | 1 | 0 | 0 | 1 | 0 |
| Double-blind Treatment Period | Lost to Follow-up | 0 | 1 | 0 | 0 | 0 | 0 |
| Double-blind Treatment Period | Moderate to Severe Opioid Withdrawal | 0 | 1 | 0 | 0 | 0 | 0 |
| Double-blind Treatment Period | Other | 0 | 0 | 0 | 0 | 2 | 1 |
| Double-blind Treatment Period | Physician Decision | 2 | 0 | 0 | 0 | 0 | 0 |
| Double-blind Treatment Period | Sponsor Decision | 0 | 1 | 0 | 0 | 1 | 0 |
| Double-blind Treatment Period | Withdrawal by Subject | 2 | 0 | 0 | 1 | 0 | 3 |
| Follow-up Period | Adverse Event | 0 | 0 | 0 | 0 | 0 | 1 |
| Follow-up Period | Other | 1 | 0 | 0 | 0 | 0 | 0 |
| Single-blind Placebo run-in Period | Adverse Event | 0 | 0 | 0 | 1 | 0 | 1 |
| Single-blind Placebo run-in Period | Inclusion/Exclusion Criteria Not Met | 0 | 1 | 1 | 0 | 0 | 0 |
| Single-blind Placebo run-in Period | Lost to Follow-up | 1 | 0 | 0 | 0 | 0 | 0 |
| Single-blind Placebo run-in Period | Other - Not specified | 1 | 0 | 0 | 0 | 1 | 1 |
| Single-blind Placebo run-in Period | Sponsor Decision | 0 | 0 | 1 | 0 | 1 | 0 |
| Single-blind Placebo run-in Period | Withdrawal by Subject | 2 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo 5 mg | NKTR-118 5 mg | Placebo 25 mg | NKTR-118 25 mg | Placebo 50 mg | NKTR-118 50 mg | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 47.5 Years STANDARD_DEVIATION 12 | 50.3 Years STANDARD_DEVIATION 13.1 | 51.0 Years STANDARD_DEVIATION 13.2 | 51.8 Years STANDARD_DEVIATION 11.4 | 48.4 Years STANDARD_DEVIATION 10.2 | 49.6 Years STANDARD_DEVIATION 11 | 49.7 Years STANDARD_DEVIATION 11.7 |
| Race/Ethnicity, Customized Black | 4 Participants | 3 Participants | 3 Participants | 2 Participants | 4 Participants | 5 Participants | 21 Participants |
| Race/Ethnicity, Customized Caucasian | 27 Participants | 28 Participants | 23 Participants | 26 Participants | 31 Participants | 25 Participants | 160 Participants |
| Race/Ethnicity, Customized Hispanic/Latino | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Not Allowed to Ask | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Female | 19 Participants | 19 Participants | 18 Participants | 15 Participants | 23 Participants | 21 Participants | 115 Participants |
| Sex: Female, Male Male | 12 Participants | 12 Participants | 9 Participants | 14 Participants | 14 Participants | 9 Participants | 70 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 19 / 30 | 18 / 33 | 26 / 35 | 15 / 27 | 15 / 32 | 13 / 37 |
| serious Total, serious adverse events | 1 / 30 | 1 / 33 | 1 / 35 | 0 / 27 | 1 / 32 | 1 / 37 |
Outcome results
Primary
Change From Baseline in Spontaneous Bowel Movements (SBMs) Per Week During Week 1
Change from baseline in SBMs/week during Week 1 was defined as SBMs/week during the first week of double-blind study medication (between Visit 4 and Visit 6) minus baseline SBMs/week. Baseline was defined as the average SBMs/week during the 2-week OIC screening period. An SBM was defined as a BM without the use of laxatives in the previous 24 hours as recorded in the e-diary.
Time frame: Days 1 through 7
Population: The MITT analysis population consisted of all randomized patients who received at least 1 dose of double-blind study treatment, had a baseline value and Visit 6 evaluable data (where Visit 6 was the Week 1 visit during the double-blind study treatment period).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo 5 mg | Change From Baseline in Spontaneous Bowel Movements (SBMs) Per Week During Week 1 | 1.8 Number of SBMs/week | Standard Deviation 2.4 |
| NKTR-118 5 mg | Change From Baseline in Spontaneous Bowel Movements (SBMs) Per Week During Week 1 | 2.6 Number of SBMs/week | Standard Deviation 3.6 |
| Placebo 25 mg | Change From Baseline in Spontaneous Bowel Movements (SBMs) Per Week During Week 1 | 1.9 Number of SBMs/week | Standard Deviation 2.5 |
| NKTR-118 25 mg | Change From Baseline in Spontaneous Bowel Movements (SBMs) Per Week During Week 1 | 3.6 Number of SBMs/week | Standard Deviation 2.3 |
| Placebo 50 mg | Change From Baseline in Spontaneous Bowel Movements (SBMs) Per Week During Week 1 | 1.9 Number of SBMs/week | Standard Deviation 5.2 |
| NKTR-118 50 mg | Change From Baseline in Spontaneous Bowel Movements (SBMs) Per Week During Week 1 | 4.4 Number of SBMs/week | Standard Deviation 3.8 |
p-value: 0.0001Wilcoxon (Mann-Whitney)
p-value: 0.002Wilcoxon (Mann-Whitney)
p-value: 0.7781Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in Patient Assessment of Constipation-Quality of Life (PAC-QOL) Questionnaire
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 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.
Time frame: Days 1 through 28
Population: The MITT analysis population consisted of all randomized patients who received at least 1 dose of double-blind study treatment, had a baseline value and Visit 6 evaluable data (where Visit 6 was the Week 1 visit during the double-blind study treatment period).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo 5 mg | Change From Baseline in Patient Assessment of Constipation-Quality of Life (PAC-QOL) Questionnaire | Satisfaction domain | 2.6 units on a scale | Standard Deviation 1.1 |
| Placebo 5 mg | Change From Baseline in Patient Assessment of Constipation-Quality of Life (PAC-QOL) Questionnaire | Worries/Concerms domain | 1.5 units on a scale | Standard Deviation 1.1 |
| Placebo 5 mg | Change From Baseline in Patient Assessment of Constipation-Quality of Life (PAC-QOL) Questionnaire | Physical Discomfort domain | 1.4 units on a scale | Standard Deviation 1 |
| Placebo 5 mg | Change From Baseline in Patient Assessment of Constipation-Quality of Life (PAC-QOL) Questionnaire | Total Score | 1.5 units on a scale | Standard Deviation 0.8 |
| Placebo 5 mg | Change From Baseline in Patient Assessment of Constipation-Quality of Life (PAC-QOL) Questionnaire | Psychosocial Discomfort domain | 0.8 units on a scale | Standard Deviation 0.7 |
| NKTR-118 5 mg | Change From Baseline in Patient Assessment of Constipation-Quality of Life (PAC-QOL) Questionnaire | Worries/Concerms domain | 1.3 units on a scale | Standard Deviation 0.9 |
| NKTR-118 5 mg | Change From Baseline in Patient Assessment of Constipation-Quality of Life (PAC-QOL) Questionnaire | Satisfaction domain | 2.4 units on a scale | Standard Deviation 1.1 |
| NKTR-118 5 mg | Change From Baseline in Patient Assessment of Constipation-Quality of Life (PAC-QOL) Questionnaire | Physical Discomfort domain | 1.2 units on a scale | Standard Deviation 0.8 |
| NKTR-118 5 mg | Change From Baseline in Patient Assessment of Constipation-Quality of Life (PAC-QOL) Questionnaire | Total Score | 1.3 units on a scale | Standard Deviation 0.8 |
| NKTR-118 5 mg | Change From Baseline in Patient Assessment of Constipation-Quality of Life (PAC-QOL) Questionnaire | Psychosocial Discomfort domain | 0.8 units on a scale | Standard Deviation 0.8 |
| Placebo 25 mg | Change From Baseline in Patient Assessment of Constipation-Quality of Life (PAC-QOL) Questionnaire | Worries/Concerms domain | 1.6 units on a scale | Standard Deviation 1.1 |
| Placebo 25 mg | Change From Baseline in Patient Assessment of Constipation-Quality of Life (PAC-QOL) Questionnaire | Satisfaction domain | 2.8 units on a scale | Standard Deviation 0.9 |
| Placebo 25 mg | Change From Baseline in Patient Assessment of Constipation-Quality of Life (PAC-QOL) Questionnaire | Total Score | 1.7 units on a scale | Standard Deviation 0.8 |
| Placebo 25 mg | Change From Baseline in Patient Assessment of Constipation-Quality of Life (PAC-QOL) Questionnaire | Psychosocial Discomfort domain | 1.1 units on a scale | Standard Deviation 1 |
| Placebo 25 mg | Change From Baseline in Patient Assessment of Constipation-Quality of Life (PAC-QOL) Questionnaire | Physical Discomfort domain | 1.7 units on a scale | Standard Deviation 0.9 |
| NKTR-118 25 mg | Change From Baseline in Patient Assessment of Constipation-Quality of Life (PAC-QOL) Questionnaire | Psychosocial Discomfort domain | 0.8 units on a scale | Standard Deviation 0.8 |
| NKTR-118 25 mg | Change From Baseline in Patient Assessment of Constipation-Quality of Life (PAC-QOL) Questionnaire | Physical Discomfort domain | 1.2 units on a scale | Standard Deviation 1 |
| NKTR-118 25 mg | Change From Baseline in Patient Assessment of Constipation-Quality of Life (PAC-QOL) Questionnaire | Worries/Concerms domain | 1.1 units on a scale | Standard Deviation 0.9 |
| NKTR-118 25 mg | Change From Baseline in Patient Assessment of Constipation-Quality of Life (PAC-QOL) Questionnaire | Satisfaction domain | 2.0 units on a scale | Standard Deviation 1.3 |
| NKTR-118 25 mg | Change From Baseline in Patient Assessment of Constipation-Quality of Life (PAC-QOL) Questionnaire | Total Score | 1.2 units on a scale | Standard Deviation 0.8 |
| Placebo 50 mg | Change From Baseline in Patient Assessment of Constipation-Quality of Life (PAC-QOL) Questionnaire | Satisfaction domain | 2.8 units on a scale | Standard Deviation 1.1 |
| Placebo 50 mg | Change From Baseline in Patient Assessment of Constipation-Quality of Life (PAC-QOL) Questionnaire | Physical Discomfort domain | 1.7 units on a scale | Standard Deviation 1.1 |
| Placebo 50 mg | Change From Baseline in Patient Assessment of Constipation-Quality of Life (PAC-QOL) Questionnaire | Total Score | 1.6 units on a scale | Standard Deviation 0.8 |
| Placebo 50 mg | Change From Baseline in Patient Assessment of Constipation-Quality of Life (PAC-QOL) Questionnaire | Worries/Concerms domain | 1.5 units on a scale | Standard Deviation 1 |
| Placebo 50 mg | Change From Baseline in Patient Assessment of Constipation-Quality of Life (PAC-QOL) Questionnaire | Psychosocial Discomfort domain | 1.0 units on a scale | Standard Deviation 0.9 |
| NKTR-118 50 mg | Change From Baseline in Patient Assessment of Constipation-Quality of Life (PAC-QOL) Questionnaire | Physical Discomfort domain | 1.3 units on a scale | Standard Deviation 1 |
| NKTR-118 50 mg | Change From Baseline in Patient Assessment of Constipation-Quality of Life (PAC-QOL) Questionnaire | Satisfaction domain | 2.2 units on a scale | Standard Deviation 1.1 |
| NKTR-118 50 mg | Change From Baseline in Patient Assessment of Constipation-Quality of Life (PAC-QOL) Questionnaire | Worries/Concerms domain | 1.2 units on a scale | Standard Deviation 0.8 |
| NKTR-118 50 mg | Change From Baseline in Patient Assessment of Constipation-Quality of Life (PAC-QOL) Questionnaire | Total Score | 1.3 units on a scale | Standard Deviation 0.8 |
| NKTR-118 50 mg | Change From Baseline in Patient Assessment of Constipation-Quality of Life (PAC-QOL) Questionnaire | Psychosocial Discomfort domain | 0.8 units on a scale | Standard Deviation 0.8 |
p-value: 0.5522Wilcoxon (Mann-Whitney)
p-value: 0.0589Wilcoxon (Mann-Whitney)
p-value: 0.1691Wilcoxon (Mann-Whitney)
p-value: 0.6293Wilcoxon (Mann-Whitney)
p-value: 0.0836Wilcoxon (Mann-Whitney)
p-value: 0.1155Wilcoxon (Mann-Whitney)
p-value: 0.9938Wilcoxon (Mann-Whitney)
p-value: 0.2101Wilcoxon (Mann-Whitney)
p-value: 0.4597Wilcoxon (Mann-Whitney)
p-value: 0.4822Wilcoxon (Mann-Whitney)
p-value: 0.0171Wilcoxon (Mann-Whitney)
p-value: 0.016Wilcoxon (Mann-Whitney)
p-value: 0.6857Wilcoxon (Mann-Whitney)
p-value: 0.0253Wilcoxon (Mann-Whitney)
p-value: 0.0772Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in Patient Assessment of Constipation-Symptoms (PAC-SYM) Questionnaire
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 is 0 (response is 'absent' for each item) to 4 (response is 'very severe' for each item). A negative change from baseline indicates improvement.
Time frame: Days 1 through 28
Population: The MITT analysis population consisted of all randomized patients who received at least 1 dose of double-blind study treatment, had a baseline value and Visit 6 evaluable data (where Visit 6 was the Week 1 visit during the double-blind study treatment period).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo 5 mg | Change From Baseline in Patient Assessment of Constipation-Symptoms (PAC-SYM) Questionnaire | Abdominal Symptoms domain | 1.2 units on a scale | Standard Deviation 0.8 |
| Placebo 5 mg | Change From Baseline in Patient Assessment of Constipation-Symptoms (PAC-SYM) Questionnaire | Rectal Symptoms domain | 0.7 units on a scale | Standard Deviation 0.8 |
| Placebo 5 mg | Change From Baseline in Patient Assessment of Constipation-Symptoms (PAC-SYM) Questionnaire | Stool Symptoms domain | 1.5 units on a scale | Standard Deviation 1 |
| Placebo 5 mg | Change From Baseline in Patient Assessment of Constipation-Symptoms (PAC-SYM) Questionnaire | Total Score | 1.2 units on a scale | Standard Deviation 0.8 |
| NKTR-118 5 mg | Change From Baseline in Patient Assessment of Constipation-Symptoms (PAC-SYM) Questionnaire | Total Score | 1.2 units on a scale | Standard Deviation 0.7 |
| NKTR-118 5 mg | Change From Baseline in Patient Assessment of Constipation-Symptoms (PAC-SYM) Questionnaire | Stool Symptoms domain | 1.5 units on a scale | Standard Deviation 0.8 |
| NKTR-118 5 mg | Change From Baseline in Patient Assessment of Constipation-Symptoms (PAC-SYM) Questionnaire | Abdominal Symptoms domain | 1.1 units on a scale | Standard Deviation 0.9 |
| NKTR-118 5 mg | Change From Baseline in Patient Assessment of Constipation-Symptoms (PAC-SYM) Questionnaire | Rectal Symptoms domain | 0.7 units on a scale | Standard Deviation 0.7 |
| Placebo 25 mg | Change From Baseline in Patient Assessment of Constipation-Symptoms (PAC-SYM) Questionnaire | Stool Symptoms domain | 1.7 units on a scale | Standard Deviation 0.8 |
| Placebo 25 mg | Change From Baseline in Patient Assessment of Constipation-Symptoms (PAC-SYM) Questionnaire | Rectal Symptoms domain | 0.8 units on a scale | Standard Deviation 0.8 |
| Placebo 25 mg | Change From Baseline in Patient Assessment of Constipation-Symptoms (PAC-SYM) Questionnaire | Abdominal Symptoms domain | 1.4 units on a scale | Standard Deviation 0.9 |
| Placebo 25 mg | Change From Baseline in Patient Assessment of Constipation-Symptoms (PAC-SYM) Questionnaire | Total Score | 1.4 units on a scale | Standard Deviation 0.6 |
| NKTR-118 25 mg | Change From Baseline in Patient Assessment of Constipation-Symptoms (PAC-SYM) Questionnaire | Rectal Symptoms domain | 0.7 units on a scale | Standard Deviation 0.8 |
| NKTR-118 25 mg | Change From Baseline in Patient Assessment of Constipation-Symptoms (PAC-SYM) Questionnaire | Abdominal Symptoms domain | 1.1 units on a scale | Standard Deviation 0.9 |
| NKTR-118 25 mg | Change From Baseline in Patient Assessment of Constipation-Symptoms (PAC-SYM) Questionnaire | Stool Symptoms domain | 1.2 units on a scale | Standard Deviation 0.9 |
| NKTR-118 25 mg | Change From Baseline in Patient Assessment of Constipation-Symptoms (PAC-SYM) Questionnaire | Total Score | 1.1 units on a scale | Standard Deviation 0.8 |
| Placebo 50 mg | Change From Baseline in Patient Assessment of Constipation-Symptoms (PAC-SYM) Questionnaire | Total Score | 1.5 units on a scale | Standard Deviation 1 |
| Placebo 50 mg | Change From Baseline in Patient Assessment of Constipation-Symptoms (PAC-SYM) Questionnaire | Rectal Symptoms domain | 1.2 units on a scale | Standard Deviation 1 |
| Placebo 50 mg | Change From Baseline in Patient Assessment of Constipation-Symptoms (PAC-SYM) Questionnaire | Abdominal Symptoms domain | 1.2 units on a scale | Standard Deviation 1 |
| Placebo 50 mg | Change From Baseline in Patient Assessment of Constipation-Symptoms (PAC-SYM) Questionnaire | Stool Symptoms domain | 1.8 units on a scale | Standard Deviation 1.1 |
| NKTR-118 50 mg | Change From Baseline in Patient Assessment of Constipation-Symptoms (PAC-SYM) Questionnaire | Rectal Symptoms domain | 0.7 units on a scale | Standard Deviation 0.8 |
| NKTR-118 50 mg | Change From Baseline in Patient Assessment of Constipation-Symptoms (PAC-SYM) Questionnaire | Stool Symptoms domain | 1.2 units on a scale | Standard Deviation 0.9 |
| NKTR-118 50 mg | Change From Baseline in Patient Assessment of Constipation-Symptoms (PAC-SYM) Questionnaire | Total Score | 1.1 units on a scale | Standard Deviation 0.9 |
| NKTR-118 50 mg | Change From Baseline in Patient Assessment of Constipation-Symptoms (PAC-SYM) Questionnaire | Abdominal Symptoms domain | 1.3 units on a scale | Standard Deviation 1 |
p-value: 0.5008Wilcoxon (Mann-Whitney)
p-value: 0.1823Wilcoxon (Mann-Whitney)
p-value: 0.7045Wilcoxon (Mann-Whitney)
p-value: 0.7088Wilcoxon (Mann-Whitney)
p-value: 0.5828Wilcoxon (Mann-Whitney)
p-value: 0.0116Wilcoxon (Mann-Whitney)
p-value: 0.7848Wilcoxon (Mann-Whitney)
p-value: 0.0335Wilcoxon (Mann-Whitney)
p-value: 0.0591Wilcoxon (Mann-Whitney)
p-value: 0.9317Wilcoxon (Mann-Whitney)
p-value: 0.0675Wilcoxon (Mann-Whitney)
p-value: 0.1745Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in SBMs/Week Across the 28-day Double-blind Period
Change from baseline in SBMs/week across the 28-day double-blind period was calculated as SBMs/week during 28-day double-blind study treatment period minus baseline SBMs/week. Baseline was defined as the average SBMs/week during the 2-week OIC screening period.
Time frame: Days 1 through 28
Population: The MITT analysis population consisted of all randomized patients who received at least 1 dose of double-blind study treatment, had a baseline value and Visit 6 evaluable data (where Visit 6 was the Week 1 visit during the double-blind study treatment period).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo 5 mg | Change From Baseline in SBMs/Week Across the 28-day Double-blind Period | 1.7 Number of SBMs/week | Standard Deviation 1.9 |
| NKTR-118 5 mg | Change From Baseline in SBMs/Week Across the 28-day Double-blind Period | 2.3 Number of SBMs/week | Standard Deviation 2.9 |
| Placebo 25 mg | Change From Baseline in SBMs/Week Across the 28-day Double-blind Period | 1.7 Number of SBMs/week | Standard Deviation 2.2 |
| NKTR-118 25 mg | Change From Baseline in SBMs/Week Across the 28-day Double-blind Period | 3.2 Number of SBMs/week | Standard Deviation 2 |
| Placebo 50 mg | Change From Baseline in SBMs/Week Across the 28-day Double-blind Period | 1.2 Number of SBMs/week | Standard Deviation 2 |
| NKTR-118 50 mg | Change From Baseline in SBMs/Week Across the 28-day Double-blind Period | 4.6 Number of SBMs/week | Standard Deviation 3.4 |
p-value: 0.5118Wilcoxon (Mann-Whitney)
p-value: 0.0022Wilcoxon (Mann-Whitney)
p-value: <0.0001Wilcoxon (Mann-Whitney)