Trial Outcomes & Findings for Effect of Ileal Bile Acid Transporter Inhibitor in Functional Constipation (NCT NCT01038687)

Last Updated: 2020-09-04

Results Overview

Subjects ingested a Technetium-99m sulfur colloid radiolabeled meal and Indium-111 absorbed on to activated charcoal particles and delivered to the colon by an oral methacrylate-coated capsule. Colonic transit was measured by quantification of radioactive counts via abdominal scintiscans. Overall colonic transit was computed as the colonic geometric center (GC), which is the weighted average of counts in the different colonic regions (ascending, transverse, descending, rectosigmoid and stool), respectively numbered 1 to 5. At any time point, the GC equals the proportion of counts in each colonic region multiplied by its weighting factor: (%ACx1+%TCx2+%DCx3+%RSx4+%stoolx5)/100. As such, a higher GC reflects faster colonic transit. A GC of 1 implies all the isotope is in the ascending colon and a GC of 5 implies all the isotope is in the stool.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

36 participants

Primary outcome timeframe

24 hours post-radiolabeled meal

Results posted on

2020-09-04

Participant Flow

Participant milestones

Participant milestones
Measure	A3309 15 mg Patients randomized to this arm received one oral tablet daily of 15 mg A3309 for a period of 14 consecutive days. A3309: A3390, a bile acid transport inhibitor was provided in either 15 mg or 20 mg oral tablets	A3309 20 mg Patients randomized to this arm received one oral tablet daily of 20 mg A3309 for a period of 14 consecutive days. A3309: A3390, a bile acid transport inhibitor was provided in either 15 mg or 20 mg oral tablets	Placebo Patients randomized to this arm received one oral tablet daily of a matching placebo for a period of 14 consecutive days. placebo: placebo
Overall Study STARTED	12	11	13
Overall Study COMPLETED	12	9	12
Overall Study NOT COMPLETED	0	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	A3309 15 mg Patients randomized to this arm received one oral tablet daily of 15 mg A3309 for a period of 14 consecutive days. A3309: A3390, a bile acid transport inhibitor was provided in either 15 mg or 20 mg oral tablets	A3309 20 mg Patients randomized to this arm received one oral tablet daily of 20 mg A3309 for a period of 14 consecutive days. A3309: A3390, a bile acid transport inhibitor was provided in either 15 mg or 20 mg oral tablets	Placebo Patients randomized to this arm received one oral tablet daily of a matching placebo for a period of 14 consecutive days. placebo: placebo
Overall Study Adverse Event	0	2	1

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	A3309 15 mg n=12 Participants Patients randomized to this arm received one oral tablet daily of 15 mg A3309 for a period of 14 consecutive days. A3309: A3390, a bile acid transport inhibitor was provided in either 15 mg or 20 mg oral tablets	A3309 20 mg n=11 Participants Patients randomized to this arm received one oral tablet daily of 20 mg A3309 for a period of 14 consecutive days. A3309: A3390, a bile acid transport inhibitor was provided in either 15 mg or 20 mg oral tablets	Placebo n=13 Participants Patients randomized to this arm received one oral tablet daily of a matching placebo for a period of 14 consecutive days. placebo: placebo	Total n=36 Participants Total of all reporting groups
Age, Continuous	38.7 years STANDARD_DEVIATION 2.4 • n=12 Participants	46.7 years STANDARD_DEVIATION 1.9 • n=11 Participants	47.5 years STANDARD_DEVIATION 2.6 • n=13 Participants	44.3 years STANDARD_DEVIATION 1.5 • n=36 Participants
Sex: Female, Male Female	12 Participants n=12 Participants	11 Participants n=11 Participants	13 Participants n=13 Participants	36 Participants n=36 Participants
Sex: Female, Male Male	0 Participants n=12 Participants	0 Participants n=11 Participants	0 Participants n=13 Participants	0 Participants n=36 Participants
Race and Ethnicity Not Collected	—	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment United States	12 participants n=12 Participants	11 participants n=11 Participants	13 participants n=13 Participants	36 participants n=36 Participants

PRIMARY outcome

Timeframe: 24 hours post-radiolabeled meal

Outcome measures

Outcome measures
Measure	A3309 15 mg n=12 Participants Patients randomized to this arm received one oral tablet daily of 15 mg A3309 for a period of 14 consecutive days. A3309: A3390, a bile acid transport inhibitor was provided in either 15 mg or 20 mg oral tablets	A3309 20 mg n=11 Participants Patients randomized to this arm received one oral tablet daily of 20 mg A3309 for a period of 14 consecutive days. A3309: A3390, a bile acid transport inhibitor was provided in either 15 mg or 20 mg oral tablets	Placebo n=13 Participants Patients randomized to this arm received one oral tablet daily of a matching placebo for a period of 14 consecutive days. placebo: placebo
Colonic Transit at 24 Hours	2.68 units on a scale Standard Error 0.07	3.12 units on a scale Standard Error 0.07	1.93 units on a scale Standard Error 0.09

SECONDARY outcome

Timeframe: 6 hours post-radiolabeled meal

Subjects ingested a Technetium-99m sulfur colloid radiolabeled meal and Indium-111 absorbed on to activated charcoal particles and delivered to the colon by an oral methacrylate-coated capsule. Colonic filling was measured by scintigraphy as the percentage of the radiolabeled meal that reached the colon at 6 hours.

Outcome measures

Outcome measures
Measure	A3309 15 mg n=12 Participants Patients randomized to this arm received one oral tablet daily of 15 mg A3309 for a period of 14 consecutive days. A3309: A3390, a bile acid transport inhibitor was provided in either 15 mg or 20 mg oral tablets	A3309 20 mg n=11 Participants Patients randomized to this arm received one oral tablet daily of 20 mg A3309 for a period of 14 consecutive days. A3309: A3390, a bile acid transport inhibitor was provided in either 15 mg or 20 mg oral tablets	Placebo n=13 Participants Patients randomized to this arm received one oral tablet daily of a matching placebo for a period of 14 consecutive days. placebo: placebo
Colonic Filling	55.8 percentage of colonic filling Standard Error 9.3	60.0 percentage of colonic filling Standard Error 6.1	50.4 percentage of colonic filling Standard Error 9.6

SECONDARY outcome

Timeframe: post-treatment, approximately 12-14 days

Subjects ingested a Technetium-99m sulfur colloid radiolabeled meal and Indium-111 absorbed on to activated charcoal particles and delivered to the colon by an oral methacrylate-coated capsule. Gastric emptying (GE t 1/2) was measured by scintigraphy and defined as the time required for 50% of the radiolabeled tracer to empty from the stomach.

Outcome measures

Outcome measures
Measure	A3309 15 mg n=12 Participants Patients randomized to this arm received one oral tablet daily of 15 mg A3309 for a period of 14 consecutive days. A3309: A3390, a bile acid transport inhibitor was provided in either 15 mg or 20 mg oral tablets	A3309 20 mg n=11 Participants Patients randomized to this arm received one oral tablet daily of 20 mg A3309 for a period of 14 consecutive days. A3309: A3390, a bile acid transport inhibitor was provided in either 15 mg or 20 mg oral tablets	Placebo n=13 Participants Patients randomized to this arm received one oral tablet daily of a matching placebo for a period of 14 consecutive days. placebo: placebo
Gastric Emptying , T1/2	165.4 minutes Standard Error 14.4	159.4 minutes Standard Error 12.8	130.8 minutes Standard Error 5.9

SECONDARY outcome

Timeframe: post-treatment, approximately 12-14 days

Subjects ingested a Technetium-99m sulfur colloid radiolabeled meal and Indium-111 absorbed on to activated charcoal particles and delivered to the colon by an oral methacrylate-coated capsule. Ascending colon emptying t 1/2 was measured by scintigraphy and defined as the time required for 50% of the radiolabeled tracer to empty from the ascending colon.

Outcome measures

Outcome measures
Measure	A3309 15 mg n=12 Participants Patients randomized to this arm received one oral tablet daily of 15 mg A3309 for a period of 14 consecutive days. A3309: A3390, a bile acid transport inhibitor was provided in either 15 mg or 20 mg oral tablets	A3309 20 mg n=11 Participants Patients randomized to this arm received one oral tablet daily of 20 mg A3309 for a period of 14 consecutive days. A3309: A3390, a bile acid transport inhibitor was provided in either 15 mg or 20 mg oral tablets	Placebo n=13 Participants Patients randomized to this arm received one oral tablet daily of a matching placebo for a period of 14 consecutive days. placebo: placebo
Ascending Colon Emptying t 1/2	14.0 hours Standard Error 3.6	5.8 hours Standard Error 1.9	14.8 hours Standard Error 1.6

SECONDARY outcome

Timeframe: 8 hours post-radiolabeled meal

Outcome measures

Outcome measures
Measure	A3309 15 mg n=12 Participants Patients randomized to this arm received one oral tablet daily of 15 mg A3309 for a period of 14 consecutive days. A3309: A3390, a bile acid transport inhibitor was provided in either 15 mg or 20 mg oral tablets	A3309 20 mg n=11 Participants Patients randomized to this arm received one oral tablet daily of 20 mg A3309 for a period of 14 consecutive days. A3309: A3390, a bile acid transport inhibitor was provided in either 15 mg or 20 mg oral tablets	Placebo n=13 Participants Patients randomized to this arm received one oral tablet daily of a matching placebo for a period of 14 consecutive days. placebo: placebo
Colonic Transit at 8 Hours	1.98 units on a scale Standard Error 0.55	2.82 units on a scale Standard Error 0.55	1.20 units on a scale Standard Error 0.09

SECONDARY outcome

Timeframe: 48 hours post-radiolabeled meal

Outcome measures

Outcome measures
Measure	A3309 15 mg n=12 Participants Patients randomized to this arm received one oral tablet daily of 15 mg A3309 for a period of 14 consecutive days. A3309: A3390, a bile acid transport inhibitor was provided in either 15 mg or 20 mg oral tablets	A3309 20 mg n=11 Participants Patients randomized to this arm received one oral tablet daily of 20 mg A3309 for a period of 14 consecutive days. A3309: A3390, a bile acid transport inhibitor was provided in either 15 mg or 20 mg oral tablets	Placebo n=13 Participants Patients randomized to this arm received one oral tablet daily of a matching placebo for a period of 14 consecutive days. placebo: placebo
Colonic Transit at 48 Hours	3.64 units on a scale Standard Error 0.07	3.91 units on a scale Standard Error 0.07	2.18 units on a scale Standard Error 0.09

SECONDARY outcome

Timeframe: 14 days

Subjects maintained a validated daily bowel diary and recorded the number of bowel movements each day during treatment.

Outcome measures

Outcome measures
Measure	A3309 15 mg n=12 Participants Patients randomized to this arm received one oral tablet daily of 15 mg A3309 for a period of 14 consecutive days. A3309: A3390, a bile acid transport inhibitor was provided in either 15 mg or 20 mg oral tablets	A3309 20 mg n=11 Participants Patients randomized to this arm received one oral tablet daily of 20 mg A3309 for a period of 14 consecutive days. A3309: A3390, a bile acid transport inhibitor was provided in either 15 mg or 20 mg oral tablets	Placebo n=13 Participants Patients randomized to this arm received one oral tablet daily of a matching placebo for a period of 14 consecutive days. placebo: placebo
Stool Frequency	1.33 bowel movements Standard Error 0.15	2.14 bowel movements Standard Error 0.39	1.43 bowel movements Standard Error 0.24

SECONDARY outcome

Timeframe: 14 days

Subjects maintained a validated daily bowel diary during treatment and recorded stool consistency according to the Bristol Stool Form Scale, where: 1= separate hard lumps; 2= lumpy sausage-shape; 3= cracked sausage; 4= smooth and soft sausage; 5=soft blobs; 6=mushy, fluffy pieces; 7= watery, no solid pieces.

Outcome measures

Outcome measures
Measure	A3309 15 mg n=12 Participants Patients randomized to this arm received one oral tablet daily of 15 mg A3309 for a period of 14 consecutive days. A3309: A3390, a bile acid transport inhibitor was provided in either 15 mg or 20 mg oral tablets	A3309 20 mg n=11 Participants Patients randomized to this arm received one oral tablet daily of 20 mg A3309 for a period of 14 consecutive days. A3309: A3390, a bile acid transport inhibitor was provided in either 15 mg or 20 mg oral tablets	Placebo n=13 Participants Patients randomized to this arm received one oral tablet daily of a matching placebo for a period of 14 consecutive days. placebo: placebo
Stool Consistency	4.17 units on a scale Standard Error 0.32	4.42 units on a scale Standard Error 0.32	2.69 units on a scale Standard Error 0.24

SECONDARY outcome

Timeframe: Day 14

Subject perception of treatment efficacy was measured using a 5 point numerical scale where 1=not at all effective to 5=extremely effective.

Outcome measures

Outcome measures
Measure	A3309 15 mg n=12 Participants Patients randomized to this arm received one oral tablet daily of 15 mg A3309 for a period of 14 consecutive days. A3309: A3390, a bile acid transport inhibitor was provided in either 15 mg or 20 mg oral tablets	A3309 20 mg n=11 Participants Patients randomized to this arm received one oral tablet daily of 20 mg A3309 for a period of 14 consecutive days. A3309: A3390, a bile acid transport inhibitor was provided in either 15 mg or 20 mg oral tablets	Placebo n=13 Participants Patients randomized to this arm received one oral tablet daily of a matching placebo for a period of 14 consecutive days. placebo: placebo
Treatment Effectiveness of A3309	3.7 score on a scale Standard Error 0.3	2.4 score on a scale Standard Error 0.4	4.3 score on a scale Standard Error 0.3

Adverse Events

A3309 15 mg

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

A3309 20 mg

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Michael Camilleri, MD

Mayo Clinic

Phone: 507-266-2305

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	A3309 15 mg n=12 participants at risk Patients randomized to this arm received one oral tablet daily of 15 mg A3309 for a period of 14 consecutive days. A3309: A3390, a bile acid transport inhibitor was provided in either 15 mg or 20 mg oral tablets	A3309 20 mg n=11 participants at risk Patients randomized to this arm received one oral tablet daily of 20 mg A3309 for a period of 14 consecutive days. A3309: A3390, a bile acid transport inhibitor was provided in either 15 mg or 20 mg oral tablets	Placebo n=13 participants at risk Patients randomized to this arm received one oral tablet daily of a matching placebo for a period of 14 consecutive days. placebo: placebo
Gastrointestinal disorders Abdominal cramps/pain	33.3% 4/12 • Number of events 4 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.	54.5% 6/11 • Number of events 6 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.	0.00% 0/13 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.
Gastrointestinal disorders Diarrhea	8.3% 1/12 • Number of events 1 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.	36.4% 4/11 • Number of events 4 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.	7.7% 1/13 • Number of events 1 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.
Gastrointestinal disorders Nausea	8.3% 1/12 • Number of events 1 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.	18.2% 2/11 • Number of events 2 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.	15.4% 2/13 • Number of events 2 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.
Gastrointestinal disorders Flatulence	8.3% 1/12 • Number of events 1 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.	9.1% 1/11 • Number of events 1 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.	15.4% 2/13 • Number of events 2 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.
Gastrointestinal disorders Borboygmi	16.7% 2/12 • Number of events 2 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.	9.1% 1/11 • Number of events 1 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.	0.00% 0/13 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.
Gastrointestinal disorders Stomach upset	0.00% 0/12 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.	9.1% 1/11 • Number of events 1 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.	7.7% 1/13 • Number of events 1 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.
General disorders Hemorrhoid pain	0.00% 0/12 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.	9.1% 1/11 • Number of events 1 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.	0.00% 0/13 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.
Gastrointestinal disorders Constipation exacerbation	0.00% 0/12 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.	0.00% 0/11 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.	7.7% 1/13 • Number of events 1 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.
General disorders Bloating	0.00% 0/12 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.	9.1% 1/11 • Number of events 1 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.	0.00% 0/13 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.
Gastrointestinal disorders Heartburn	8.3% 1/12 • Number of events 1 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.	0.00% 0/11 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.	0.00% 0/13 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.
General disorders Stress	0.00% 0/12 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.	0.00% 0/11 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.	15.4% 2/13 • Number of events 2 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.
General disorders Sinusitis	0.00% 0/12 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.	0.00% 0/11 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.	30.8% 4/13 • Number of events 4 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.
General disorders Headache	0.00% 0/12 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.	0.00% 0/11 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.	76.9% 10/13 • Number of events 10 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.
General disorders Lightheadness	0.00% 0/12 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.	0.00% 0/11 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.	15.4% 2/13 • Number of events 2 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.
General disorders Lethargy	8.3% 1/12 • Number of events 1 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.	0.00% 0/11 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.	0.00% 0/13 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.
General disorders Chills	8.3% 1/12 • Number of events 1 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.	0.00% 0/11 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.	0.00% 0/13 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.
General disorders Body ache	8.3% 1/12 • Number of events 1 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.	0.00% 0/11 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.	0.00% 0/13 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.
Renal and urinary disorders Urinary Tract Infection	0.00% 0/12 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.	9.1% 1/11 • Number of events 1 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.	0.00% 0/13 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.
Nervous system disorders Paresthesia	0.00% 0/12 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.	9.1% 1/11 • Number of events 1 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.	0.00% 0/13 • Adverse events were collected on each subject from enrollment until 7-10 days after the last day of the study medication, for approximately one month.