Trial Outcomes & Findings for Study to Assess the Effect Of Alosetron On Mucosal Blood Flow (NCT NCT00370032)
NCT ID: NCT00370032
Last Updated: 2015-05-18
Results Overview
On Day 6 of each treatment period; 1 hour after dosing, subjects underwent a flexible sigmoidoscopy with Laser Doppler Flowmetry (LDF) to measure Mucosal Blood Flow (MBF). There were no pre-treatment LDF procedure, MBF was compared between the Healthy volunteers and D-irritable bowel syndrome (IBS) cohorts using the flow rates from the placebo treatment period.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
49 participants
Primary outcome timeframe
Day 6 after each treatment period
Results posted on
2015-05-18
Participant Flow
Participant milestones
| Measure |
d-IBS (Diarrhea Predominant - Irritable Bowel Syndrome)
Subjects with diarrhea-predominant irritable bowel syndrome. This group was randomize to EITHER 0.5 mg BID Alosetron or Placebo for 6 days followed by a flexible sigmoidoscopy; followed by a 7 day washout period; Then the subjects who were given study drug the first treatment period were given Placebo and vice versa for the next 6 days followed by a flexible sigmoidoscopy then had a 7 day follow up period.
|
Healthy Volunteers
Subjects with no clinical disease. This group was randomize to EITHER 0.5 mg BID Alosetron or Placebo for 6 days followed by flexible sigmoidoscopy then had a 7 day washout period; Then the subjects who were given study drug the first treatment period were given Placebo and vice versa for the next 6 days followed by another 7 day wash out period and a 7 day follow up period.
|
|---|---|---|
|
Treatment Period 1
STARTED
|
24
|
25
|
|
Treatment Period 1
COMPLETED
|
24
|
24
|
|
Treatment Period 1
NOT COMPLETED
|
0
|
1
|
|
Washout Period
STARTED
|
24
|
24
|
|
Washout Period
COMPLETED
|
23
|
22
|
|
Washout Period
NOT COMPLETED
|
1
|
2
|
|
Treatment Period 2
STARTED
|
23
|
22
|
|
Treatment Period 2
COMPLETED
|
23
|
22
|
|
Treatment Period 2
NOT COMPLETED
|
0
|
0
|
|
Follow-up Period
STARTED
|
23
|
22
|
|
Follow-up Period
COMPLETED
|
22
|
22
|
|
Follow-up Period
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
d-IBS (Diarrhea Predominant - Irritable Bowel Syndrome)
Subjects with diarrhea-predominant irritable bowel syndrome. This group was randomize to EITHER 0.5 mg BID Alosetron or Placebo for 6 days followed by a flexible sigmoidoscopy; followed by a 7 day washout period; Then the subjects who were given study drug the first treatment period were given Placebo and vice versa for the next 6 days followed by a flexible sigmoidoscopy then had a 7 day follow up period.
|
Healthy Volunteers
Subjects with no clinical disease. This group was randomize to EITHER 0.5 mg BID Alosetron or Placebo for 6 days followed by flexible sigmoidoscopy then had a 7 day washout period; Then the subjects who were given study drug the first treatment period were given Placebo and vice versa for the next 6 days followed by another 7 day wash out period and a 7 day follow up period.
|
|---|---|---|
|
Treatment Period 1
Unable to perform sigmoidoscopy on Day 6
|
0
|
1
|
|
Washout Period
Withdrawal by Subject
|
0
|
1
|
|
Washout Period
Lost to Follow-up
|
0
|
1
|
|
Washout Period
Adverse Event
|
1
|
0
|
|
Follow-up Period
Withdrawal by Subject
|
1
|
0
|
Baseline Characteristics
Study to Assess the Effect Of Alosetron On Mucosal Blood Flow
Baseline characteristics by cohort
| Measure |
d-IBS
n=22 Participants
Diarrhea-predominant irritable bowel syndrome. This group was randomize to EITHER 0.5 mb BID Alosetron or Placebo for 6 days followed by a flexible sigmoidoscopy; followed by a 7 day washout period; Then the subjects who were given study drug the first treatment period were given Placebo and vice versa for the next 6 days followed by another wash out period and a 7 day follow up period.
|
Healthy Volunteers
n=22 Participants
Volunteers without clinical disease. This group was randomize to EITHER 0.5 mb BID Alosetron or Placebo for 6 days followed by a flexible sigmoidoscopy; followed by a 7 day washout period; Then the subjects who were given study drug the first treatment period were given Placebo and vice versa for the next 6 days followed by another wash out period and a 7 day follow up period.
|
Total
n=44 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
33.2 years
STANDARD_DEVIATION 8.8 • n=5 Participants
|
26.9 years
STANDARD_DEVIATION 5.8 • n=7 Participants
|
29.99 years
STANDARD_DEVIATION 7.42 • n=5 Participants
|
|
Sex: Female, Male
Female
|
22 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
44 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White/Caucasian/European
|
17 participants
n=5 Participants
|
16 participants
n=7 Participants
|
33 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
African American
|
3 participants
n=5 Participants
|
2 participants
n=7 Participants
|
5 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Central/South Asian
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
2 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
East Asian
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
South East Asian
|
0 participants
n=5 Participants
|
2 participants
n=7 Participants
|
2 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Mixed Race
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 6 after each treatment periodPopulation: Per Protocol Population - the population used for the primary and secondary outcome analyses. The population consisted of all randomized subjects who completed the study with MBF measurements for both treatment periods.
On Day 6 of each treatment period; 1 hour after dosing, subjects underwent a flexible sigmoidoscopy with Laser Doppler Flowmetry (LDF) to measure Mucosal Blood Flow (MBF). There were no pre-treatment LDF procedure, MBF was compared between the Healthy volunteers and D-irritable bowel syndrome (IBS) cohorts using the flow rates from the placebo treatment period.
Outcome measures
| Measure |
d-IBS Placebo
n=22 Participants
Subjects with diarrhea-predominant irritable bowel syndrome. In Treatment Period 1 this group was first randomized to Placebo for 6 days followed by a flexible sigmoidoscopy; followed by a 7 day washout period; Then, in Treatment Period 2 the subjects were given Alosetron 0.5 mg (BID)for 5 days and on the 6th day one dose and a flexible sigmoidoscopy; followed by another wash out period of 7 days and a 7 day follow up period.
|
d-IBS Alosetron
n=22 Participants
Subjects with diarrhea-predominant irritable bowel syndrome. In Treatment Period 1, this group was randomized to 0.5 mb BID Alosetron for 5days and 1 dose on the 6th day followed by a flexible sigmoidoscopy; followed by a 7 day washout period; Then, in Treatment Period 2 the subjects were given Placebo for the next 6 days followed by another 7 day wash out period and a 7 day follow up period.
|
Healthy Volunteers Placebo
n=19 Participants
Subjects without Clinical disease. In Treatment Period 1 this group was first randomized to Placebo for 6 days followed by a flexible sigmoidoscopy; followed by a 7 day washout period; Then, in Treatment Period 2 the subjects were given Alosetron 0.5 mg (BID)for 5 days and on the 6th day one dose and a flexible sigmoidoscopy; followed by another wash out period of 7 days and a 7 day follow up period.
|
Healthy Volunteers Alosetron
n=19 Participants
Subjects without clinical disease. In Treatment Period 1 this group was randomized to 0.5 mb BID Alosetron for 5days and 1 dose on the 6th day followed by a flexible sigmoidoscopy; followed by a 7 day washout period; Then,in Treatment Period 2 the subjects were given Placebo for the next 6 days followed by another 7 day wash out period and a 7 day follow up period.
|
|---|---|---|---|---|
|
Left Colon Mucosal Blood Flow (MBF)
|
125.6 ml per minute per 100 grams of tissue
Standard Deviation 38.6
|
117.5 ml per minute per 100 grams of tissue
Standard Deviation 37.71
|
130.7 ml per minute per 100 grams of tissue
Standard Deviation 40.12
|
121.6 ml per minute per 100 grams of tissue
Standard Deviation 51.26
|
SECONDARY outcome
Timeframe: Day 6 after each treatment periodOn Day 6 of each treatment period approximately 1 hour after dosing, subjects underwent a flexible sigmoidoscopy with Laser Doppler Flowmetry (LDF) to measure Mucosal Blood Flow (MBF). There was no pre-treatment LDF procedure, MBF was compared between the Healthy and d-IBS cohorts using the flow rates from the placebo treatment period.
Outcome measures
| Measure |
d-IBS Placebo
n=22 Participants
Subjects with diarrhea-predominant irritable bowel syndrome. In Treatment Period 1 this group was first randomized to Placebo for 6 days followed by a flexible sigmoidoscopy; followed by a 7 day washout period; Then, in Treatment Period 2 the subjects were given Alosetron 0.5 mg (BID)for 5 days and on the 6th day one dose and a flexible sigmoidoscopy; followed by another wash out period of 7 days and a 7 day follow up period.
|
d-IBS Alosetron
n=22 Participants
Subjects with diarrhea-predominant irritable bowel syndrome. In Treatment Period 1, this group was randomized to 0.5 mb BID Alosetron for 5days and 1 dose on the 6th day followed by a flexible sigmoidoscopy; followed by a 7 day washout period; Then, in Treatment Period 2 the subjects were given Placebo for the next 6 days followed by another 7 day wash out period and a 7 day follow up period.
|
Healthy Volunteers Placebo
n=22 Participants
Subjects without Clinical disease. In Treatment Period 1 this group was first randomized to Placebo for 6 days followed by a flexible sigmoidoscopy; followed by a 7 day washout period; Then, in Treatment Period 2 the subjects were given Alosetron 0.5 mg (BID)for 5 days and on the 6th day one dose and a flexible sigmoidoscopy; followed by another wash out period of 7 days and a 7 day follow up period.
|
Healthy Volunteers Alosetron
n=22 Participants
Subjects without clinical disease. In Treatment Period 1 this group was randomized to 0.5 mb BID Alosetron for 5days and 1 dose on the 6th day followed by a flexible sigmoidoscopy; followed by a 7 day washout period; Then,in Treatment Period 2 the subjects were given Placebo for the next 6 days followed by another 7 day wash out period and a 7 day follow up period.
|
|---|---|---|---|---|
|
Rectal Mucosal Blood Flow (MBF)
|
173 ml per minute per 100 grams of tissue
Standard Deviation 45.52
|
159.1 ml per minute per 100 grams of tissue
Standard Deviation 51.73
|
149.1 ml per minute per 100 grams of tissue
Standard Deviation 39.82
|
140.3 ml per minute per 100 grams of tissue
Standard Deviation 56
|
SECONDARY outcome
Timeframe: Day 6 after each treatment periodPopulation: Population: modified per protocol to include placebo information only.
On Day 6 of each treatment period approximately 1 hour after dosing, subjects underwent a flexible sigmoidoscopy with Laser Doppler Flowmetry (LDF) to measure Mucosal Blood Flow (MBF). There was no pre-treatment LDF procedure, MBF was compared between the Healthy and d-IBS cohorts using the flow rates from the placebo treatment period.
Outcome measures
| Measure |
d-IBS Placebo
n=22 Participants
Subjects with diarrhea-predominant irritable bowel syndrome. In Treatment Period 1 this group was first randomized to Placebo for 6 days followed by a flexible sigmoidoscopy; followed by a 7 day washout period; Then, in Treatment Period 2 the subjects were given Alosetron 0.5 mg (BID)for 5 days and on the 6th day one dose and a flexible sigmoidoscopy; followed by another wash out period of 7 days and a 7 day follow up period.
|
d-IBS Alosetron
n=22 Participants
Subjects with diarrhea-predominant irritable bowel syndrome. In Treatment Period 1, this group was randomized to 0.5 mb BID Alosetron for 5days and 1 dose on the 6th day followed by a flexible sigmoidoscopy; followed by a 7 day washout period; Then, in Treatment Period 2 the subjects were given Placebo for the next 6 days followed by another 7 day wash out period and a 7 day follow up period.
|
Healthy Volunteers Placebo
n=19 Participants
Subjects without Clinical disease. In Treatment Period 1 this group was first randomized to Placebo for 6 days followed by a flexible sigmoidoscopy; followed by a 7 day washout period; Then, in Treatment Period 2 the subjects were given Alosetron 0.5 mg (BID)for 5 days and on the 6th day one dose and a flexible sigmoidoscopy; followed by another wash out period of 7 days and a 7 day follow up period.
|
Healthy Volunteers Alosetron
n=22 Participants
Subjects without clinical disease. In Treatment Period 1 this group was randomized to 0.5 mb BID Alosetron for 5days and 1 dose on the 6th day followed by a flexible sigmoidoscopy; followed by a 7 day washout period; Then,in Treatment Period 2 the subjects were given Placebo for the next 6 days followed by another 7 day wash out period and a 7 day follow up period.
|
|---|---|---|---|---|
|
Left Colon and Rectal Mucosal Blood Flow Cohort Comparisons
|
135.1 ml per minute per 100 grams of tissue
Standard Deviation 38.6
|
178.9 ml per minute per 100 grams of tissue
Standard Deviation 45.52
|
149.9 ml per minute per 100 grams of tissue
Standard Deviation 40.12
|
166.6 ml per minute per 100 grams of tissue
Standard Deviation 39.82
|
Adverse Events
d-IBS Placebo
Serious events: 0 serious events
Other events: 12 other events
Deaths: 0 deaths
d-IBS Alosetron
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Healthy Volunteers Placebo
Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths
Healthy Volunteers Alosetron
Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
d-IBS Placebo
n=24 participants at risk
Diarrhea-predominant irritable bowel syndrome. Participants receiving 0.5 mb Placebo BID in either the first or second 6-day treatment period. Both treatment periods were followed by a 7-day washout period; the second washout period was followed by a 7-day follow up period.
|
d-IBS Alosetron
n=23 participants at risk
Diarrhea-predominant irritable bowel syndrome. Participants receiving 0.5 mb Alosetron BID in either the first or second 6-day treatment period. Both treatment periods were followed by a 7-day washout period; the second washout period was followed by a 7-day follow up period.
|
Healthy Volunteers Placebo
n=24 participants at risk
Volunteers without clinical disease. Participants receiving 0.5 mb Placebo BID in either the first or second 6-day treatment period. Both treatment periods were followed by a 7-day washout period; the second washout period was followed by a 7-day follow up period.
|
Healthy Volunteers Alosetron
n=23 participants at risk
Volunteers without clinical disease. Participants receiving 0.5 mb Alosetron BID in either the first or second 6-day treatment period. Both treatment periods were followed by a 7-day washout period; the second washout period was followed by a 7-day follow up period.
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Abdominal Distention
|
4.2%
1/24
|
0.00%
0/23
|
4.2%
1/24
|
13.0%
3/23
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
4.2%
1/24
|
4.3%
1/23
|
4.2%
1/24
|
8.7%
2/23
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/24
|
17.4%
4/23
|
0.00%
0/24
|
4.3%
1/23
|
|
Gastrointestinal disorders
Diarrhoea
|
8.3%
2/24
|
0.00%
0/23
|
4.2%
1/24
|
0.00%
0/23
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/24
|
4.3%
1/23
|
0.00%
0/24
|
4.3%
1/23
|
|
Gastrointestinal disorders
Flatulence
|
4.2%
1/24
|
0.00%
0/23
|
0.00%
0/24
|
4.3%
1/23
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/24
|
8.7%
2/23
|
0.00%
0/24
|
0.00%
0/23
|
|
Gastrointestinal disorders
Vomiting
|
4.2%
1/24
|
0.00%
0/23
|
0.00%
0/24
|
0.00%
0/23
|
|
Infections and infestations
Rhinitis
|
8.3%
2/24
|
13.0%
3/23
|
12.5%
3/24
|
8.7%
2/23
|
|
Infections and infestations
Acarodermatitis
|
4.2%
1/24
|
0.00%
0/23
|
0.00%
0/24
|
0.00%
0/23
|
|
Infections and infestations
Lower respiratory tract infection
|
0.00%
0/24
|
0.00%
0/23
|
4.2%
1/24
|
0.00%
0/23
|
|
Nervous system disorders
Headache
|
8.3%
2/24
|
0.00%
0/23
|
12.5%
3/24
|
13.0%
3/23
|
|
Nervous system disorders
Dizziness
|
8.3%
2/24
|
4.3%
1/23
|
0.00%
0/24
|
0.00%
0/23
|
|
Nervous system disorders
Lethargy
|
4.2%
1/24
|
0.00%
0/23
|
0.00%
0/24
|
0.00%
0/23
|
|
Nervous system disorders
Migraine
|
4.2%
1/24
|
0.00%
0/23
|
0.00%
0/24
|
0.00%
0/23
|
|
Nervous system disorders
Somnolence
|
4.2%
1/24
|
0.00%
0/23
|
0.00%
0/24
|
0.00%
0/23
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/24
|
0.00%
0/23
|
8.3%
2/24
|
4.3%
1/23
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/24
|
0.00%
0/23
|
4.2%
1/24
|
0.00%
0/23
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/24
|
0.00%
0/23
|
4.2%
1/24
|
0.00%
0/23
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/24
|
4.3%
1/23
|
0.00%
0/24
|
0.00%
0/23
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/24
|
4.3%
1/23
|
0.00%
0/24
|
0.00%
0/23
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/24
|
0.00%
0/23
|
4.2%
1/24
|
0.00%
0/23
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
4.2%
1/24
|
0.00%
0/23
|
0.00%
0/24
|
0.00%
0/23
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
0.00%
0/24
|
0.00%
0/23
|
4.2%
1/24
|
0.00%
0/23
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.00%
0/24
|
0.00%
0/23
|
4.2%
1/24
|
0.00%
0/23
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
8.3%
2/24
|
0.00%
0/23
|
0.00%
0/24
|
0.00%
0/23
|
|
Skin and subcutaneous tissue disorders
Rash
|
4.2%
1/24
|
4.3%
1/23
|
0.00%
0/24
|
0.00%
0/23
|
|
Skin and subcutaneous tissue disorders
Rash pruritic
|
0.00%
0/24
|
0.00%
0/23
|
4.2%
1/24
|
0.00%
0/23
|
|
Respiratory, thoracic and mediastinal disorders
Urticaria
|
4.2%
1/24
|
0.00%
0/23
|
0.00%
0/24
|
0.00%
0/23
|
|
Reproductive system and breast disorders
Dysmenorrhoea
|
0.00%
0/24
|
0.00%
0/23
|
4.2%
1/24
|
4.3%
1/23
|
|
Reproductive system and breast disorders
Metrorrhagia
|
4.2%
1/24
|
0.00%
0/23
|
0.00%
0/24
|
0.00%
0/23
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/24
|
0.00%
0/23
|
0.00%
0/24
|
4.3%
1/23
|
|
Psychiatric disorders
Insomnia
|
4.2%
1/24
|
0.00%
0/23
|
0.00%
0/24
|
0.00%
0/23
|
|
General disorders
Pyrexia
|
0.00%
0/24
|
0.00%
0/23
|
4.2%
1/24
|
0.00%
0/23
|
|
Renal and urinary disorders
Micturition disorder
|
0.00%
0/24
|
4.3%
1/23
|
0.00%
0/24
|
0.00%
0/23
|
|
Renal and urinary disorders
Micturition urgency
|
0.00%
0/24
|
4.3%
1/23
|
0.00%
0/24
|
0.00%
0/23
|
Additional Information
GSK Response Center
GlaxoSmithKline
Phone: 866-435-7343
Results disclosure agreements
- Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
- Publication restrictions are in place
Restriction type: OTHER