Trial Outcomes & Findings for Evaluation of the Efficacy and Safety of ADL5945 for the Treatment of Opioid-induced Constipation in Adults Taking Opioid Therapy for Chronic Noncancer Pain (NCT NCT01207427)
NCT ID: NCT01207427
Last Updated: 2018-09-25
Results Overview
An SBM was defined as a bowel movement (BM) with no laxative use in the previous 24 hours. Each weekly SBM average was calculated as follows: (7 × number of SBMs) / (number of days with nonmissing data). The overall SBM rate for the 4-week double-blind treatment period was calculated as follows: (the average of the first week + the average of the second week + the average of the third week + the average of the fourth week) / 4.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
131 participants
Primary outcome timeframe
Baseline, Weeks 1 through 4 of treatment
Results posted on
2018-09-25
Participant Flow
Participant milestones
| Measure |
ADL5945 0.1 mg
During the Run-in Placebo Period, each participant received 1 placebo capsule orally BID for 1 week. Then during the Double-blind Treatment Period, each participant received one 0.1-milligrams (mg) ADL5945 capsule orally BID for 4 weeks. Then during the Run-out Placebo Period, each participant received 1 placebo capsule orally BID for 1 week.
|
ADL5945 0.25 mg
During the Run-in Placebo Period, each participant received 1 placebo capsule orally BID for 1 week. Then during the Double-blind Treatment Period, each participant received one 0.25-mg ADL5945 capsule orally BID for 4 weeks. Then during the Run-out Placebo Period, each participant received 1 placebo capsule orally BID for 1 week.
|
Placebo
Each participant received 1 placebo capsule orally twice daily (BID) during the Run-in Placebo Period (1 week), the Double-blind Treatment Period (4 weeks), and the Run-out Placebo Period (1 week).
|
|---|---|---|---|
|
Run-in Placebo Period
STARTED
|
43
|
45
|
43
|
|
Run-in Placebo Period
COMPLETED
|
43
|
45
|
43
|
|
Run-in Placebo Period
NOT COMPLETED
|
0
|
0
|
0
|
|
Double-blind Treatment Period
STARTED
|
43
|
45
|
43
|
|
Double-blind Treatment Period
Received at Least 1 Dose of Study Drug
|
43
|
45
|
43
|
|
Double-blind Treatment Period
COMPLETED
|
40
|
43
|
41
|
|
Double-blind Treatment Period
NOT COMPLETED
|
3
|
2
|
2
|
|
Run-out Placebo Period
STARTED
|
40
|
43
|
41
|
|
Run-out Placebo Period
COMPLETED
|
40
|
43
|
41
|
|
Run-out Placebo Period
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
ADL5945 0.1 mg
During the Run-in Placebo Period, each participant received 1 placebo capsule orally BID for 1 week. Then during the Double-blind Treatment Period, each participant received one 0.1-milligrams (mg) ADL5945 capsule orally BID for 4 weeks. Then during the Run-out Placebo Period, each participant received 1 placebo capsule orally BID for 1 week.
|
ADL5945 0.25 mg
During the Run-in Placebo Period, each participant received 1 placebo capsule orally BID for 1 week. Then during the Double-blind Treatment Period, each participant received one 0.25-mg ADL5945 capsule orally BID for 4 weeks. Then during the Run-out Placebo Period, each participant received 1 placebo capsule orally BID for 1 week.
|
Placebo
Each participant received 1 placebo capsule orally twice daily (BID) during the Run-in Placebo Period (1 week), the Double-blind Treatment Period (4 weeks), and the Run-out Placebo Period (1 week).
|
|---|---|---|---|
|
Double-blind Treatment Period
Adverse Event
|
0
|
1
|
0
|
|
Double-blind Treatment Period
Lost to Follow-up
|
0
|
0
|
1
|
|
Double-blind Treatment Period
Protocol Violation
|
2
|
1
|
1
|
|
Double-blind Treatment Period
Withdrawal by Subject
|
1
|
0
|
0
|
Baseline Characteristics
Evaluation of the Efficacy and Safety of ADL5945 for the Treatment of Opioid-induced Constipation in Adults Taking Opioid Therapy for Chronic Noncancer Pain
Baseline characteristics by cohort
| Measure |
ADL5945 0.1 mg
n=43 Participants
During the Run-in Placebo Period, each participant received 1 placebo capsule orally BID for 1 week. Then during the Double-blind Treatment Period, each participant received one 0.1 mg ADL5945 capsule orally BID for 4 weeks. Then during the Run-out Placebo Period, each participant received 1 placebo capsule orally BID for 1 week.
|
ADL5945 0.25 mg
n=45 Participants
During the Run-in Placebo Period, each participant received 1 placebo capsule orally BID for 1 week. Then during the Double-blind Treatment Period, each participant received one 0.25-mg ADL5945 capsule orally BID for 4 weeks. Then during the Run-out Placebo Period, each participant received 1 placebo capsule orally BID for 1 week.
|
Placebo
n=43 Participants
Each participant received 1 placebo capsule orally twice daily (BID) during the Run-in Placebo Period (1 week), the Double-blind Treatment Period (4 weeks), and the Run-out Placebo Period (1 week).
|
Total
n=131 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
LTE18
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age, Categorical
BTWN
|
40 Participants
n=5 Participants
|
44 Participants
n=7 Participants
|
40 Participants
n=5 Participants
|
124 Participants
n=4 Participants
|
|
Age, Categorical
GTE65
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
|
Sex: Female, Male
Female
|
20 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
63 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
23 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
68 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline, Weeks 1 through 4 of treatmentPopulation: All participants who were randomized to study treatment and had at least 1 evaluable SBM post-dose measurement during the Double-blind Period. Last-observation-carried-forward (LOCF) was used to impute missing postbaseline values.
An SBM was defined as a bowel movement (BM) with no laxative use in the previous 24 hours. Each weekly SBM average was calculated as follows: (7 × number of SBMs) / (number of days with nonmissing data). The overall SBM rate for the 4-week double-blind treatment period was calculated as follows: (the average of the first week + the average of the second week + the average of the third week + the average of the fourth week) / 4.
Outcome measures
| Measure |
ADL5945 0.1 mg
n=43 Participants
During the Run-in Placebo Period, each participant received 1 placebo capsule orally BID for 1 week. Then during the Double-blind Treatment Period, each participant received one 0.1-mg ADL5945 capsule orally BID for 4 weeks. Then during the Run-out Placebo Period, each participant received 1 placebo capsule orally BID for 1 week.
|
ADL5945 0.25 mg
n=45 Participants
During the Run-in Placebo Period, each participant received 1 placebo capsule orally BID for 1 week. Then during the Double-blind Treatment Period, each participant received one 0.25-mg ADL5945 capsule orally BID for 4 weeks. Then during the Run-out Placebo Period, each participant received 1 placebo capsule orally BID for 1 week.
|
Placebo
n=43 Participants
Each participant received 1 placebo capsule orally twice daily (BID) during the Run-in Placebo Period (1 week), the Double-blind Treatment Period (4 weeks), and the Run-out Placebo Period (1 week).
|
|---|---|---|---|
|
Change From Baseline in the Weekly Average of Spontaneous Bowel Movements (SBMs) During Treatment
|
1.96 Number of SBMs/week
Standard Error 0.35
|
3.42 Number of SBMs/week
Standard Error 0.49
|
1.44 Number of SBMs/week
Standard Error 0.27
|
Adverse Events
ADL5945 0.1 mg
Serious events: 0 serious events
Other events: 14 other events
Deaths: 0 deaths
ADL5945 0.25 mg
Serious events: 2 serious events
Other events: 19 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 15 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
ADL5945 0.1 mg
n=43 participants at risk
During the Run-in Placebo Period, each participant received 1 placebo capsule orally BID for 1 week. Then during the Double-blind Treatment Period, each participant received one 0.1- mg ADL5945 capsule orally BID for 4 weeks. Then during the Run-out Placebo Period, each participant received 1 placebo capsule orally BID for 1 week.
|
ADL5945 0.25 mg
n=45 participants at risk
During the Run-in Placebo Period, each participant received 1 placebo capsule orally BID for 1 week. Then during the Double-blind Treatment Period, each participant received one 0.25-mg ADL5945 capsule orally BID for 4 weeks. Then during the Run-out Placebo Period, each participant received 1 placebo capsule orally BID for 1 week.
|
Placebo
n=43 participants at risk
Each participant received 1 placebo capsule orally twice daily (BID) during the Run-in Placebo Period (1 week), the Double-blind Treatment Period (4 weeks), and the Run-out Placebo Period (1 week).
|
|---|---|---|---|
|
Cardiac disorders
Myocardial Infarction
|
0.00%
0/43
|
2.2%
1/45 • Number of events 1
|
0.00%
0/43
|
|
Respiratory, thoracic and mediastinal disorders
Chronic Obstructive Pulmonary Disease
|
0.00%
0/43
|
2.2%
1/45 • Number of events 1
|
0.00%
0/43
|
Other adverse events
| Measure |
ADL5945 0.1 mg
n=43 participants at risk
During the Run-in Placebo Period, each participant received 1 placebo capsule orally BID for 1 week. Then during the Double-blind Treatment Period, each participant received one 0.1- mg ADL5945 capsule orally BID for 4 weeks. Then during the Run-out Placebo Period, each participant received 1 placebo capsule orally BID for 1 week.
|
ADL5945 0.25 mg
n=45 participants at risk
During the Run-in Placebo Period, each participant received 1 placebo capsule orally BID for 1 week. Then during the Double-blind Treatment Period, each participant received one 0.25-mg ADL5945 capsule orally BID for 4 weeks. Then during the Run-out Placebo Period, each participant received 1 placebo capsule orally BID for 1 week.
|
Placebo
n=43 participants at risk
Each participant received 1 placebo capsule orally twice daily (BID) during the Run-in Placebo Period (1 week), the Double-blind Treatment Period (4 weeks), and the Run-out Placebo Period (1 week).
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Leukocytosis
|
0.00%
0/43
|
2.2%
1/45 • Number of events 1
|
0.00%
0/43
|
|
Cardiac disorders
Acute Coronary Syndrome
|
0.00%
0/43
|
2.2%
1/45 • Number of events 1
|
0.00%
0/43
|
|
Cardiac disorders
Atrial Fibrillation
|
0.00%
0/43
|
2.2%
1/45 • Number of events 1
|
0.00%
0/43
|
|
Cardiac disorders
Mitral Valve Incompetence
|
0.00%
0/43
|
2.2%
1/45 • Number of events 1
|
0.00%
0/43
|
|
Cardiac disorders
Palpitations
|
0.00%
0/43
|
2.2%
1/45 • Number of events 1
|
0.00%
0/43
|
|
Gastrointestinal disorders
Abdominal Pain
|
4.7%
2/43 • Number of events 2
|
2.2%
1/45 • Number of events 1
|
2.3%
1/43 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
2.3%
1/43 • Number of events 1
|
0.00%
0/45
|
0.00%
0/43
|
|
Gastrointestinal disorders
Diarrhoea
|
2.3%
1/43 • Number of events 1
|
0.00%
0/45
|
0.00%
0/43
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/43
|
0.00%
0/45
|
2.3%
1/43 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/43
|
2.2%
1/45 • Number of events 1
|
2.3%
1/43 • Number of events 2
|
|
Gastrointestinal disorders
Oral Discomfort
|
2.3%
1/43 • Number of events 1
|
0.00%
0/45
|
0.00%
0/43
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/43
|
2.2%
1/45 • Number of events 1
|
2.3%
1/43 • Number of events 1
|
|
Gastrointestinal disorders
Vomiting
|
2.3%
1/43 • Number of events 1
|
2.2%
1/45 • Number of events 1
|
0.00%
0/43
|
|
General disorders
Adverse Drug Reaction
|
2.3%
1/43 • Number of events 1
|
0.00%
0/45
|
0.00%
0/43
|
|
General disorders
Drug Withdrawal Syndrome
|
0.00%
0/43
|
2.2%
1/45 • Number of events 1
|
0.00%
0/43
|
|
General disorders
Pain
|
0.00%
0/43
|
2.2%
1/45 • Number of events 1
|
2.3%
1/43 • Number of events 1
|
|
Infections and infestations
Acute Sinusitis
|
0.00%
0/43
|
0.00%
0/45
|
2.3%
1/43 • Number of events 1
|
|
Infections and infestations
Bronchitis
|
2.3%
1/43 • Number of events 1
|
2.2%
1/45 • Number of events 1
|
0.00%
0/43
|
|
Infections and infestations
Gastroenteritis
|
2.3%
1/43 • Number of events 1
|
2.2%
1/45 • Number of events 1
|
2.3%
1/43 • Number of events 1
|
|
Infections and infestations
Laryngitis
|
2.3%
1/43 • Number of events 1
|
0.00%
0/45
|
0.00%
0/43
|
|
Infections and infestations
Paronychia
|
2.3%
1/43 • Number of events 1
|
0.00%
0/45
|
0.00%
0/43
|
|
Infections and infestations
Sinusitis
|
0.00%
0/43
|
0.00%
0/45
|
2.3%
1/43 • Number of events 1
|
|
Infections and infestations
Tooth Infection
|
0.00%
0/43
|
2.2%
1/45 • Number of events 1
|
0.00%
0/43
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
7.0%
3/43 • Number of events 3
|
11.1%
5/45 • Number of events 5
|
14.0%
6/43 • Number of events 6
|
|
Infections and infestations
Urinary Tract Infection
|
4.7%
2/43 • Number of events 2
|
2.2%
1/45 • Number of events 1
|
0.00%
0/43
|
|
Infections and infestations
Vulvovaginal Mycotic Infection
|
0.00%
0/20
|
5.0%
1/20 • Number of events 1
|
0.00%
0/23
|
|
Infections and infestations
Wound Infection
|
0.00%
0/43
|
0.00%
0/45
|
2.3%
1/43 • Number of events 1
|
|
Injury, poisoning and procedural complications
Animal Bite
|
2.3%
1/43 • Number of events 1
|
0.00%
0/45
|
0.00%
0/43
|
|
Injury, poisoning and procedural complications
Ankle Fracture
|
2.3%
1/43 • Number of events 1
|
0.00%
0/45
|
0.00%
0/43
|
|
Injury, poisoning and procedural complications
Burns First Degree
|
0.00%
0/43
|
2.2%
1/45 • Number of events 1
|
0.00%
0/43
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/43
|
0.00%
0/45
|
2.3%
1/43 • Number of events 1
|
|
Injury, poisoning and procedural complications
Road Traffic Accident
|
0.00%
0/43
|
2.2%
1/45 • Number of events 1
|
0.00%
0/43
|
|
Injury, poisoning and procedural complications
Sunburn
|
0.00%
0/43
|
2.2%
1/45 • Number of events 1
|
0.00%
0/43
|
|
Injury, poisoning and procedural complications
Wound Dehiscence
|
0.00%
0/43
|
0.00%
0/45
|
2.3%
1/43 • Number of events 1
|
|
Investigations
Alanine Aminotransferase Increased
|
4.7%
2/43 • Number of events 2
|
4.4%
2/45 • Number of events 2
|
2.3%
1/43 • Number of events 1
|
|
Investigations
Aspartate Aminotransferase Increased
|
2.3%
1/43 • Number of events 1
|
2.2%
1/45 • Number of events 1
|
2.3%
1/43 • Number of events 1
|
|
Investigations
Blood Alkaline Phosphatase Increased
|
0.00%
0/43
|
2.2%
1/45 • Number of events 1
|
0.00%
0/43
|
|
Investigations
Gamma-Glutamyltransferase Increased
|
4.7%
2/43 • Number of events 2
|
2.2%
1/45 • Number of events 1
|
0.00%
0/43
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
2.3%
1/43 • Number of events 1
|
2.2%
1/45 • Number of events 1
|
0.00%
0/43
|
|
Nervous system disorders
Dizziness
|
0.00%
0/43
|
2.2%
1/45 • Number of events 1
|
0.00%
0/43
|
|
Nervous system disorders
Headache
|
2.3%
1/43 • Number of events 2
|
4.4%
2/45 • Number of events 2
|
0.00%
0/43
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/43
|
2.2%
1/45 • Number of events 1
|
0.00%
0/43
|
|
Skin and subcutaneous tissue disorders
Ecchymosis
|
0.00%
0/43
|
0.00%
0/45
|
2.3%
1/43 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Night Sweats
|
0.00%
0/43
|
2.2%
1/45 • Number of events 1
|
0.00%
0/43
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/43
|
2.2%
1/45 • Number of events 1
|
0.00%
0/43
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/43
|
2.2%
1/45 • Number of events 1
|
0.00%
0/43
|
|
Vascular disorders
Hot Flush
|
0.00%
0/43
|
2.2%
1/45 • Number of events 1
|
0.00%
0/43
|
Additional Information
Vice President Clinical Research
Cubist Pharmaceuticals
Phone: (781) 860-8660
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER