Chronic Constipation, Constipation
Conditions
Keywords
Chronic idiopathic constipation, A3309
Brief summary
The purpose of this trial is to determine the efficacy and safety of A3309 administered to patients with chronic idiopathic constipation.
Interventions
DRUGA3309
A3309 in three different dosage levels or placebo once daily for the duration of the study
Sponsors
Albireo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Patient meets protocol specified criteria for constipation * Patient has successfully completed study requirements with no clinically relevant findings for physical exam, ECG, laboratory tests and colonoscopy as applicable
Exclusion criteria
* Medical history or medical condition that would not make the patient a good candidate for the study or limit the patient´s ability to complete the study * Patient reports loose stools * Patient has IBS with pain/discomfort as predominant symptom * Patient needs medications prohibited as specified in the protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Frequency of Spontaneous Bowel Movements | Baseline, weekly, up to 8 weeks | Primary ep W 1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Responder Analyses for Complete Spontaneous Bowel Movements (CSBMs) | Baseline, weekly and up to 8 weeks | A CSBM responder is defined as per FDA draft guidance for IBS-C: An increase of one or more of CSBMs per week over baseline for at least 4 out of the 8 weeks of treatment |
| Time to First Bowel Movement | First week | — |
| Stool Consistency Change From Baseline | Baseline, weekly and up to 8 weeks | Bristol Stool Form Scale. Min value:1. Max value: 7. Higher value indicates more liquid shape than normal, lower indicates constipated state. |
| LDL/HDL Ratio | Baseline and 8 weeks of treatment | Ratio of plasma LDL cholesterol and HDL cholesterol Difference from baseline, placebo-adjusted |
| Straining Change From Baseline | Baseline and during 8 weeks of treatment | Daily assessment of straining. Min value: 1. Max value: 5. Higher value indicates more straining. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Elobixibat (A3309) 5 mg Administered once daily for the duration of the study | 48 |
| Elobixibat (A3309) 10 mg Administered once daily for the duration of the study. | 47 |
| Elobixibat (A3309) 15 mg Administered once daily for the duration of the study | 48 |
| Placebo Administered once daily for the duration of the study | 47 |
| Total | 190 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 4 | 7 | 1 |
| Overall Study | Lack of Efficacy | 1 | 0 | 1 | 4 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 |
| Overall Study | Protocol Violation | 1 | 1 | 2 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Elobixibat (A3309) 10 mg | Total | Placebo | Elobixibat (A3309) 15 mg | Elobixibat (A3309) 5 mg |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 16 Participants | 6 Participants | 5 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 46 Participants | 174 Participants | 41 Participants | 43 Participants | 44 Participants |
| Age, Continuous | 48 years STANDARD_DEVIATION 11 | 48 years STANDARD_DEVIATION 12 | 50 years STANDARD_DEVIATION 13 | 46 years STANDARD_DEVIATION 13 | 48 years STANDARD_DEVIATION 13 |
| Region of Enrollment United States | 47 participants | 190 participants | 47 participants | 48 participants | 48 participants |
| Sex: Female, Male Female | 45 Participants | 170 Participants | 39 Participants | 43 Participants | 43 Participants |
| Sex: Female, Male Male | 2 Participants | 20 Participants | 8 Participants | 5 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 48 | 5 / 47 | 13 / 48 | 3 / 47 |
| serious Total, serious adverse events | 1 / 48 | 1 / 47 | 0 / 48 | 1 / 47 |
Outcome results
Primary
Change From Baseline in Frequency of Spontaneous Bowel Movements
Primary ep W 1
Time frame: Baseline, weekly, up to 8 weeks
Population: ITT population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Elobixibat (A3309) 5 mg | Change From Baseline in Frequency of Spontaneous Bowel Movements | 2.5 Number of SBMs | Standard Error 0.7 |
| Elobixibat (A3309) 10 mg | Change From Baseline in Frequency of Spontaneous Bowel Movements | 4.0 Number of SBMs | Standard Error 0.7 |
| Elobixibat (A3309) 15 mg | Change From Baseline in Frequency of Spontaneous Bowel Movements | 5.4 Number of SBMs | Standard Error 0.71 |
| Placebo | Change From Baseline in Frequency of Spontaneous Bowel Movements | 1.7 Number of SBMs | Standard Error 0.7 |
p-value: <0.2ANCOVA
p-value: 0.002ANCOVA
p-value: <0.001ANCOVA
Secondary
LDL/HDL Ratio
Ratio of plasma LDL cholesterol and HDL cholesterol Difference from baseline, placebo-adjusted
Time frame: Baseline and 8 weeks of treatment
Population: ITT population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Elobixibat (A3309) 5 mg | LDL/HDL Ratio | -0.10 Ratio | Standard Error 0.08 |
| Elobixibat (A3309) 10 mg | LDL/HDL Ratio | -0.27 Ratio | Standard Error 0.09 |
| Elobixibat (A3309) 15 mg | LDL/HDL Ratio | -0.21 Ratio | Standard Error 0.1 |
Comparison: Comparison vs placebop-value: 0.01ANCOVA
Comparison: Comparison vs placebop-value: <0.05ANCOVA
Secondary
Responder Analyses for Complete Spontaneous Bowel Movements (CSBMs)
A CSBM responder is defined as per FDA draft guidance for IBS-C: An increase of one or more of CSBMs per week over baseline for at least 4 out of the 8 weeks of treatment
Time frame: Baseline, weekly and up to 8 weeks
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Elobixibat (A3309) 5 mg | Responder Analyses for Complete Spontaneous Bowel Movements (CSBMs) | 25 participants |
| Elobixibat (A3309) 10 mg | Responder Analyses for Complete Spontaneous Bowel Movements (CSBMs) | 27 participants |
| Elobixibat (A3309) 15 mg | Responder Analyses for Complete Spontaneous Bowel Movements (CSBMs) | 30 participants |
| Placebo | Responder Analyses for Complete Spontaneous Bowel Movements (CSBMs) | 14 participants |
p-value: 0.03Fisher Exact
p-value: 0.008Fisher Exact
p-value: <0.001Fisher Exact
Secondary
Stool Consistency Change From Baseline
Bristol Stool Form Scale. Min value:1. Max value: 7. Higher value indicates more liquid shape than normal, lower indicates constipated state.
Time frame: Baseline, weekly and up to 8 weeks
Population: ITT population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Elobixibat (A3309) 5 mg | Stool Consistency Change From Baseline | 0.91 units on a scale (1-7) | Standard Deviation 0.99 |
| Elobixibat (A3309) 10 mg | Stool Consistency Change From Baseline | 1.52 units on a scale (1-7) | Standard Deviation 1.2 |
| Elobixibat (A3309) 15 mg | Stool Consistency Change From Baseline | 1.91 units on a scale (1-7) | Standard Deviation 1.3 |
| Placebo | Stool Consistency Change From Baseline | 0.66 units on a scale (1-7) | Standard Deviation 1 |
p-value: 0.44ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
Secondary
Straining Change From Baseline
Daily assessment of straining. Min value: 1. Max value: 5. Higher value indicates more straining.
Time frame: Baseline and during 8 weeks of treatment
Population: ITT population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Elobixibat (A3309) 5 mg | Straining Change From Baseline | -0.84 units on a scale (1-5) | Standard Error 0.1 |
| Elobixibat (A3309) 10 mg | Straining Change From Baseline | -1.13 units on a scale (1-5) | Standard Error 0.1 |
| Elobixibat (A3309) 15 mg | Straining Change From Baseline | -1.15 units on a scale (1-5) | Standard Error 0.1 |
| Placebo | Straining Change From Baseline | -0.64 units on a scale (1-5) | Standard Error 0.1 |
p-value: 0.17ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
Secondary
Time to First Bowel Movement
Time frame: First week
Population: ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Elobixibat (A3309) 5 mg | Time to First Bowel Movement | 23 hours |
| Elobixibat (A3309) 10 mg | Time to First Bowel Movement | 12 hours |
| Elobixibat (A3309) 15 mg | Time to First Bowel Movement | 7 hours |
| Placebo | Time to First Bowel Movement | 27 hours |
p-value: 0.06Fisher Exact
p-value: 0.03Fisher Exact
p-value: 0.04Fisher Exact