Trial Outcomes & Findings for Efficacy of To Be Marketed (TBM) Cholic Acid Capsules Used to Treat Children With Inborn Errors of Bile Acid Synthesis (NCT NCT01115582)

NCT ID: NCT01115582

Last Updated: 2023-10-03

Results Overview

Concentration of serum alanine transaminase (ALT) and aspartate transaminase (AST)

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 16 participants
• Primary outcome timeframe: At baseline and after 30 days of treatment
• Results posted on: 2023-10-03

Participant Flow

In this single-arm study, patients served as their own controls: Reference was presented by the baseline value, when patients received cholic acid capsules prepared by the Cincinnati Children's Hospital Medical Center; Investigational Treatment was the to-be-marketed (TBM) cholic acid capsule administered to patients for 30 days treatment duration.

The study was performed in patients with inborn defects of bile acid synthesis currently receiving cholic acid capsules prepared by the Cincinnati Children's Hospital Medical Center (CCHMC) under IND 45,470. The study planned to include 25 patients; but only 16 patients fulfilled eligibility criteria and were willing to travel to the CCHMC.

Participant milestones

Measure	Cholic Acid All patients entered and treated
Overall Study STARTED	16
Overall Study COMPLETED	16
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Efficacy of To Be Marketed (TBM) Cholic Acid Capsules Used to Treat Children With Inborn Errors of Bile Acid Synthesis

Baseline characteristics by cohort

Measure	Cholic Acid n=16 Participants All patients entered and treated
Age, Continuous	7.8 years STANDARD_DEVIATION 4.6 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants
Region of Enrollment United States	16 participants n=5 Participants

PRIMARY outcome

Timeframe: At baseline and after 30 days of treatment

Population: All patients entered and treated

Concentration of serum alanine transaminase (ALT) and aspartate transaminase (AST)

Outcome measures

Measure	Cholic Acid n=16 Participants All patients entered and treated
Serum Transaminases ALT, baseline	31.4 U/L Standard Deviation 21.9
Serum Transaminases ALT, Day 30	30.9 U/L Standard Deviation 24.0
Serum Transaminases AST, baseline	62.7 U/L Standard Deviation 27.1
Serum Transaminases AST, Day 30	65.0 U/L Standard Deviation 39.0

PRIMARY outcome

Timeframe: At baseline (BL) and after 30 days of treatment (D30)

Population: All patients entered and treated

Concentration of bile acids in serum (S) and urine (U). (abbreviations: chol.=cholenoic; monohydro=monohydroxy; dihydro=monohydro)

Outcome measures

Measure	Cholic Acid n=16 Participants All patients entered and treated
Serum and Urine Bile Acids U, BL: 3β,7α-dihydroxy-Δ5 sulfate m/z 469	12.37 mmol/L Standard Deviation 35.31
Serum and Urine Bile Acids U, D30: 3β,7α-dihydroxy-Δ5 sulfate m/z 469	2.762 mmol/L Standard Deviation 3.955
Serum and Urine Bile Acids U, BL: 3β,7α,12α-trihydroxy-Δ5 sulfate m/z 485	14.11 mmol/L Standard Deviation 42.78
Serum and Urine Bile Acids U, D30: 3β,7α,12α-trihydroxy-Δ5 sulfate m/z 485	2.011 mmol/L Standard Deviation 2.995
Serum and Urine Bile Acids U, BL: 3β,7α-dihydroxy-Δ5 gluycosulfate m/z 526	159.85 mmol/L Standard Deviation 474.52
Serum and Urine Bile Acids U, D30: 3β,7α-dihydroxy-Δ5 gluycosulfate m/z 526	19.958 mmol/L Standard Deviation 29.341
Serum and Urine Bile Acids U,BL: 3β,7α,12α-trihydroxy-Δ5 glycosulfate m/z 542	105.43 mmol/L Standard Deviation 337.05
Serum and Urine Bile Acids U,D30: 3β,7α,12α-trihydroxy-Δ5 glycosulfate m/z542	5.421 mmol/L Standard Deviation 7.633
Serum and Urine Bile Acids S,BL: Glyco-3-oxo-7-α,12α-dihydroxy-4-chol. m/z460	0.15 mmol/L Standard Deviation 0.07
Serum and Urine Bile Acids S,D30: Glyco-3-oxo-7-α,12α-dihydroxy-4-chol.m/z460	0.055 mmol/L Standard Deviation 0.078
Serum and Urine Bile Acids S,BL:Glyco-3-oxo-7-α,12α-monohydroxy-4-chol.m/z444	0.14 mmol/L Standard Deviation 0.01
Serum and Urine Bile Acids S,D30:Glyco-3-oxo-7-α,12α-monohydro.-4-chol.m/z444	0.140 mmol/L Standard Deviation 0.184
Serum and Urine Bile Acids S, BL: Tauro-3-oxo-7-α,12α-dihydroxy-4-chol.m/z510	0.52 mmol/L Standard Deviation 0.23
Serum and Urine Bile Acids S,D30: Tauro-3-oxo-7-α,12α-dihydroxy-4-chol.m/z510	0.490 mmol/L Standard Deviation 0.679
Serum and Urine Bile Acids S,BL:Tauro-3-oxo-7-α,12α-monohydroxy-4-chol.m/z498	0.05 mmol/L Standard Deviation 0.04
Serum and Urine Bile Acids S,D30:Tauro-3-oxo-7-α,12α-monohydro.-4-chol.m/z498	0.020 mmol/L Standard Deviation 0.028
Serum and Urine Bile Acids U, BL: Total 3β-hydroxy-Δ5 bile acids	291.77 mmol/L Standard Deviation 889.56
Serum and Urine Bile Acids U, D30: Total 3β-hydroxy-Δ5 bile acids	30.148 mmol/L Standard Deviation 43.582
Serum and Urine Bile Acids S, BL: Total 3-oxo-Δ4 bile acids	0.84 mmol/L Standard Deviation 0.13
Serum and Urine Bile Acids S, D30: Total 3-oxo-Δ4 bile acids	0.705 mmol/L Standard Deviation 0.601

SECONDARY outcome

Timeframe: Total of 30 days, i.e. from the time point the patients entered into the study up to the end of treatment

Population: All patients entered and treated

Total number of patients with any adverse events

Outcome measures

Measure	Cholic Acid n=16 Participants All patients entered and treated
Adverse Events	9 participants

SECONDARY outcome

Timeframe: At baseline and after 30 days of treatment

Population: All patients entered and treated

Systolic blood pressure (SBP) and diastolic blood pressure (DBP)

Outcome measures

Measure	Cholic Acid n=16 Participants All patients entered and treated
Blood Pressure SBP, baseline	106.9 mmHg Standard Deviation 10.2
Blood Pressure SBP, Day 30	109.6 mmHg Standard Deviation 6.6
Blood Pressure DBP, baseline	63.9 mmHg Standard Deviation 6.7
Blood Pressure DBP, Day 30	65.4 mmHg Standard Deviation 6.8

SECONDARY outcome

Timeframe: At baseline (BL) and after 30 days of treatment (D30)

Population: All patients entered and treated

Total number of patients with abnormal findings from general physical examination

Outcome measures

Measure	Cholic Acid n=16 Participants All patients entered and treated
Physical Examination BL, N patients with abnormal physical findings	0 participants
Physical Examination D30, N patients with abnormal physical findings	0 participants

SECONDARY outcome

Timeframe: At baseline and after 30 days of treatment

Population: All patients entered and treated

Concentration of total bilirubin in serum

Outcome measures

Measure	Cholic Acid n=16 Participants All patients entered and treated
Total Bilirubin Baseline, total bilirubin	0.35 mg/dL Standard Deviation 0.37
Total Bilirubin D30, total bilirubin	0.32 mg/dL Standard Deviation 0.28

Adverse Events

Cholic Acid

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Measure	Cholic Acid n=16 participants at risk All patients entered and treated
Gastrointestinal disorders Vomiting	6.2% 1/16 • Total of 30 days, i.e. from the time point the patients entered into the study up to the end of treatment
General disorders Fever	6.2% 1/16 • Total of 30 days, i.e. from the time point the patients entered into the study up to the end of treatment

Other adverse events

Measure	Cholic Acid n=16 participants at risk All patients entered and treated
General disorders Decreased/low 250H/Vit D	25.0% 4/16 • Total of 30 days, i.e. from the time point the patients entered into the study up to the end of treatment
General disorders Decreased Vitamin A	6.2% 1/16 • Total of 30 days, i.e. from the time point the patients entered into the study up to the end of treatment
Vascular disorders Nosebleed	6.2% 1/16 • Total of 30 days, i.e. from the time point the patients entered into the study up to the end of treatment
Gastrointestinal disorders Diarrhoea	6.2% 1/16 • Total of 30 days, i.e. from the time point the patients entered into the study up to the end of treatment
Gastrointestinal disorders Reflux	6.2% 1/16 • Total of 30 days, i.e. from the time point the patients entered into the study up to the end of treatment
Hepatobiliary disorders Increased ALT	6.2% 1/16 • Total of 30 days, i.e. from the time point the patients entered into the study up to the end of treatment
Hepatobiliary disorders Increased AST	6.2% 1/16 • Total of 30 days, i.e. from the time point the patients entered into the study up to the end of treatment
Musculoskeletal and connective tissue disorders Muscle spasm	6.2% 1/16 • Total of 30 days, i.e. from the time point the patients entered into the study up to the end of treatment

Additional Information

Retrophin Medical Information

Retrophin, Inc.

Phone: 1-877-659

Email: medinfo@retrophin.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place