PEDFIC 1: This Study Will Investigate the Efficacy and Safety of A4250 in Children With PFIC Types 1 or 2
Sponsor
Albireo (Industry)
Overall Status
Completed
CT.gov ID
NCT03566238
Collaborator
(none)
62
45
3
26.4
1.4
0.1
Study Details
Study Description
Brief Summary
Double blind, randomized, placebo controlled, Phase 3 study to investigate the efficacy and safety of low doses and high doses of A4250 compared to placebo in children with progressive familial intrahepatic cholestasis (PFIC) types 1 and 2.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
Up to 50 sites in the following countries will take part in this study:
Australia, Belgium, Canada, France, Germany, Israel, Italy, Netherlands, Poland, Spain, Sweden, Turkey, United Kingdom, United States, and Saudi Arabia
Study Design
Study Type:
Interventional
Actual Enrollment
:
62 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Double-Blind, Randomized, Placebo-ControlledDouble-Blind, Randomized, Placebo-Controlled
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Double-Blind, Randomized, Placebo-Controlled, Phase 3 Study to Demonstrate Efficacy and Safety of A4250 in Children With Progressive Familial Intrahepatic Cholestasis Types 1 and 2 (PEDFIC 1)
Actual Study Start Date
:
May 16, 2018
Actual Primary Completion Date
:
Jul 27, 2020
Actual Study Completion Date
:
Jul 28, 2020
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: A4250 low dose Capsules for oral administration (40 ug/kg) once daily for 24 weeks |
Drug: A4250 (odevixibat)
A4250 is a small molecule and selective inhibitor of ileal bile acid transporter (IBAT).
|
| Experimental: A4250 high dose Capsules for oral administration (120 ug/kg) once daily for 24 weeks |
Drug: A4250 (odevixibat)
A4250 is a small molecule and selective inhibitor of ileal bile acid transporter (IBAT).
|
| Placebo Comparator: Placebo Capsules for oral administration (to match active) once daily for 24 weeks |
Drug: Placebo
Placebo identical in appearance to active drug (A4250).
|
Outcome Measures
Primary Outcome Measures
- Proportion of Positive Pruritus Assessments at the Participant Level Over the 24-week Treatment Period Based on the Albireo Observer-reported Outcome (ObsRO) Instrument (United States Primary Endpoint) [Over 24 weeks of treatment]
ObsRO instrument was used to assess severity of observed scratching twice a day (AM and PM) with score from 0 to 4 where 0 is no scratching and 4 is worst possible scratching. A positive pruritus assessment was defined as a scratching score of <= 1 or at least one point drop from baseline. At each post baseline assessment over the 24-week treatment period, the AM score was compared to the baseline AM average and the PM score was compared to the baseline PM average. Both AM and PM pruritus assessments were included in the analysis. Any intermittently missing assessment or missing planned assessment after premature treatment discontinuation, death, or initiation of rescue treatment was classified as negative assessment. Proportion of positive pruritus assessments at the participant level over the 24-week was then calculated. Full analysis set was used for the analysis.
- Percentage of Participants Experiencing at Least a 70% Reduction in Fasting s-BA Concentration From Baseline to the End of Treatment or Reaching a Level <= 70 μmol/L After 24 Weeks of Treatment (European Union and Rest of the World Primary Endpoint) [Over 24 weeks of treatment]
Fasting s-BA baseline was calculated as the average of the last 2 values prior to the first dose. The end value was the average of the values at Weeks 22 and 24 after the start of double-blind treatment. Participants who had at least 70% reduction in Fasting s-BA from baseline to the end of treatment or reached <=70 μmol/L after 24 weeks of treatment were considered as responder. Participants with missing average at the end of treatment were classified as non-responder. Full analysis set was used for the analysis.
Eligibility Criteria
Criteria
Ages Eligible for Study:
6 Months
to 18 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Key Inclusion Criteria:
-
A male or female participant with a clinical diagnosis of PFIC Type 1 or 2 and with a body weight above 5 kg
-
Participant must have clinical genetic confirmation of PFIC-1 or PFIC-2
-
Participant must have elevated serum bile acid (s-BA) concentration
-
Participant must have history of significant pruritus and a caregiver reported observed scratching in the eDiary
-
Participant and/or legal guardian must sign informed consent (and assent) as appropriate.
-
Participants will be expected to have a consistent caregiver(s) for the duration of the study
-
Caregivers and age-appropriate participants (≥8 years of age) must be willing and able to use an eDiary device as required by the study
Key Exclusion Criteria:
-
Participant with pathologic variations of the ABCB11 gene that predict complete absence of the bile salt export pump (BSEP) protein
-
Participant with past medical history or ongoing presence of other types of liver disease including, but not limited to, the following:
-
Biliary atresia of any kind
-
Benign recurrent intrahepatic cholestasis, indicated by any history of normal s BAs
-
Suspected or proven liver cancer or metastasis to the liver on imaging studies
-
Histopathology on liver biopsy that is suggestive of alternate non-PFIC related etiology of cholestasis
-
Participant with past medical history or ongoing chronic diarrhea
-
Any participant with suspected or confirmed cancers except for basal cell carcinoma
-
Participant with a past medical history of chronic kidney disease with an impaired renal function and a glomerular filtration rate <70 mL/min/1.73 m^2
-
Participant with surgical history of disruption of the enterohepatic circulation (biliary diversion surgery) within 6 months prior to start of Screening Period
-
Participant has had a liver transplant or a liver transplant is planned within 6 months of randomization
-
Decompensated liver disease
-
Participant suffers from uncontrolled, recalcitrant pruritic condition other than PFIC
-
Participant who has been previously treated with an IBAT inhibitor whose pruritus has not responded to treatment
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Children's Hospital Los Angeles | Los Angeles | California | United States | 90027 |
| 2 | University of California, San Francisco | San Francisco | California | United States | 94143 |
| 3 | Children's Hospital Colorado | Denver | Colorado | United States | 80045 |
| 4 | Emory University School of Medicine | Atlanta | Georgia | United States | 30329 |
| 5 | Johns Hopkins School of Medicine | Baltimore | Maryland | United States | 21287 |
| 6 | Washington University School of Medicine | Saint Louis | Missouri | United States | 63110 |
| 7 | Icahn School of Medicine at Mount Sinai | New York | New York | United States | 10029 |
| 8 | Columbia University Medical Center - Presbyterian Hospital Building | New York | New York | United States | 10032 |
| 9 | Cleveland Clinic | Cleveland | Ohio | United States | 44195 |
| 10 | Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | United States | 19104 |
| 11 | Children's Hospital of Pittsburgh | Pittsburgh | Pennsylvania | United States | 15224 |
| 12 | Baylor College of Medicine - Texas Children's Liver Center | Houston | Texas | United States | 77030 |
| 13 | The Royal Children's Hospital | Melbourne | Australia | ||
| 14 | UZ Leuven | Leuven | Belgium | ||
| 15 | Cliniques Universitaires Saint-Luc | Woluwe-Saint-Lambert | Belgium | ||
| 16 | The Hospital for Sick Children | Toronto | Canada | ||
| 17 | British Columbia Children's Hospital | Vancouver | Canada | ||
| 18 | University and Pediatric Hospital of Lyon | Bron | France | ||
| 19 | Universite Paris SUD - Hopitaux Universitaires Paris-Sud - Hopital Bicetre | le Kremlin Bicetre | France | ||
| 20 | Hospital de la Timone | Marseille | France | ||
| 21 | Hospital Necker-Enfants maladies | Paris | France | ||
| 22 | Uniklinikum Essen- Kinderklinik II | Essen | Germany | ||
| 23 | Medizinische Hochschule Hannover | Hannover | Germany | ||
| 24 | Kinderklinik Tübingen, Universitätsklinikum Tübingen | Tubingen | Germany | ||
| 25 | Rambam Medical Centre | Haifa | Israel | ||
| 26 | Shaare-Zedek Mc | Jerusalem | Israel | ||
| 27 | Schneider Children's Medical Center Of Israel | Petach-Tikva | Israel | ||
| 28 | Azienda Ospedaliera Papa Giovanni XXIII | Bergamo | Italy | ||
| 29 | University Hospital Of Padova | Padova | Italy | ||
| 30 | Ospedale Regina Margherita | Torino | Italy | ||
| 31 | University Medical Center Groningen | Groningen | Netherlands | ||
| 32 | Universitair Medisch Centrum (UMC) Utrecht | Utrecht | Netherlands | ||
| 33 | Instytut Pomnik - Centrum Zdrowia Dziecka | Warsaw | Poland | ||
| 34 | King Faisal Specialist Hospital & Research Centre | Riyadh | Saudi Arabia | 11211 | |
| 35 | Hospital Universitari Vall d'Hebron | Barcelona | Spain | ||
| 36 | Hospital Universitario La Paz | Madrid | Spain | ||
| 37 | Astrid Lindgren Children's Hospital, Karolinska University Hospital | Solna | Sweden | ||
| 38 | Gazi University | Ankara | Turkey | ||
| 39 | Hacettepe University Faculty of Medicine | Ankara | Turkey | ||
| 40 | Akdeniz University | Antalya | Turkey | ||
| 41 | Istanbul University Medical Faculty | Istanbul | Turkey | ||
| 42 | Inonu University Medical Faculty | Malatya | Turkey | ||
| 43 | Birmingham Women's and Children's NHS Foundation Trust | Birmingham | United Kingdom | ||
| 44 | Leeds General Infirmary | Leeds | United Kingdom | ||
| 45 | Institute of Liver Studies - Kings College Hospital | London | United Kingdom |
Sponsors and Collaborators
- Albireo
Investigators
None specified.Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Albireo
ClinicalTrials.gov Identifier:
NCT03566238
Other Study ID Numbers:
- A4250-005
First Posted:
Jun 25, 2018
Last Update Posted:
Sep 5, 2021
Last Verified:
Aug 1, 2021
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Albireo
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | A4250 Low Dose | A4250 High Dose | Placebo |
|---|---|---|---|
| Arm/Group Description | Capsules for oral administration (40 ug/kg) once daily for 24 weeks A4250 (odevixibat): A4250 is a small molecule and selective inhibitor of IBAT. | Capsules for oral administration (120 ug/kg) once daily for 24 weeks A4250 (odevixibat): A4250 is a small molecule and selective inhibitor of IBAT. | Capsules for oral administration (to match active) once daily for 24 weeks Placebo: Placebo identical in appearance to active drug (A4250). |
| Period Title: Overall Study | |||
| STARTED | 23 | 19 | 20 |
| Received Treatment | 23 | 19 | 20 |
| COMPLETED | 18 | 16 | 15 |
| NOT COMPLETED | 5 | 3 | 5 |
Baseline Characteristics
| Arm/Group Title | A4250 Low Dose | A4250 High Dose | Placebo | Total |
|---|---|---|---|---|
| Arm/Group Description | Capsules for oral administration (40 ug/kg) once daily for 24 weeks A4250 (odevixibat): A4250 is a small molecule and selective inhibitor of IBAT. | Capsules for oral administration (120 ug/kg) once daily for 24 weeks A4250 (odevixibat): A4250 is a small molecule and selective inhibitor of IBAT. | Capsules for oral administration (to match active) once daily for 24 weeks Placebo: Placebo identical in appearance to active drug (A4250). | Total of all reporting groups |
| Overall Participants | 23 | 19 | 20 | 62 |
| Age (Count of Participants) | ||||
| <=18 years |
23
100%
|
19
100%
|
20
100%
|
62
100%
|
| Between 18 and 65 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| >=65 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
3.86
(3.660)
|
5.24
(4.188)
|
3.75
(3.853)
|
4.25
(3.883)
|
| Age, Customized (Count of Participants) | ||||
| 6 months to 5 years |
17
73.9%
|
14
73.7%
|
16
80%
|
47
75.8%
|
| 6 to 12 years |
5
21.7%
|
4
21.1%
|
3
15%
|
12
19.4%
|
| 13 to 18 years |
1
4.3%
|
1
5.3%
|
1
5%
|
3
4.8%
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
12
52.2%
|
11
57.9%
|
8
40%
|
31
50%
|
| Male |
11
47.8%
|
8
42.1%
|
12
60%
|
31
50%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||
| White |
18
78.3%
|
17
89.5%
|
17
85%
|
52
83.9%
|
| Black or African American |
2
8.7%
|
0
0%
|
0
0%
|
2
3.2%
|
| Asian |
0
0%
|
1
5.3%
|
1
5%
|
2
3.2%
|
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Other |
3
13%
|
1
5.3%
|
2
10%
|
6
9.7%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||
| Hispanic or Latino |
0
0%
|
0
0%
|
1
5%
|
1
1.6%
|
| Not Hispanic or Latino |
23
100%
|
19
100%
|
19
95%
|
61
98.4%
|
| Region of Enrollment (participants) [Number] | ||||
| United States |
2
8.7%
|
3
15.8%
|
3
15%
|
8
12.9%
|
| United Kingdom |
6
26.1%
|
2
10.5%
|
5
25%
|
13
21%
|
| Saudi Arabia |
0
0%
|
2
10.5%
|
1
5%
|
3
4.8%
|
| Canada |
1
4.3%
|
0
0%
|
1
5%
|
2
3.2%
|
| Netherlands |
0
0%
|
2
10.5%
|
1
5%
|
3
4.8%
|
| Turkey |
7
30.4%
|
3
15.8%
|
1
5%
|
11
17.7%
|
| Poland |
0
0%
|
1
5.3%
|
2
10%
|
3
4.8%
|
| Italy |
1
4.3%
|
0
0%
|
1
5%
|
2
3.2%
|
| Israel |
0
0%
|
1
5.3%
|
1
5%
|
2
3.2%
|
| France |
3
13%
|
1
5.3%
|
1
5%
|
5
8.1%
|
| Australia |
0
0%
|
0
0%
|
1
5%
|
1
1.6%
|
| Germany |
3
13%
|
4
21.1%
|
2
10%
|
9
14.5%
|
| Type of Progressive Familial Intrahepatic Cholestasis (PFIC) (Count of Participants) | ||||
| Type 1 |
7
30.4%
|
5
26.3%
|
5
25%
|
17
27.4%
|
| Type 2 |
16
69.6%
|
14
73.7%
|
15
75%
|
45
72.6%
|
Outcome Measures
| Title | Proportion of Positive Pruritus Assessments at the Participant Level Over the 24-week Treatment Period Based on the Albireo Observer-reported Outcome (ObsRO) Instrument (United States Primary Endpoint) |
|---|---|
| Description | ObsRO instrument was used to assess severity of observed scratching twice a day (AM and PM) with score from 0 to 4 where 0 is no scratching and 4 is worst possible scratching. A positive pruritus assessment was defined as a scratching score of <= 1 or at least one point drop from baseline. At each post baseline assessment over the 24-week treatment period, the AM score was compared to the baseline AM average and the PM score was compared to the baseline PM average. Both AM and PM pruritus assessments were included in the analysis. Any intermittently missing assessment or missing planned assessment after premature treatment discontinuation, death, or initiation of rescue treatment was classified as negative assessment. Proportion of positive pruritus assessments at the participant level over the 24-week was then calculated. Full analysis set was used for the analysis. |
| Time Frame | Over 24 weeks of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set (FAS) included all randomized participants who received at least 1 dose of study treatment. |
| Arm/Group Title | A4250 Low Dose | A4250 High Dose | Placebo |
|---|---|---|---|
| Arm/Group Description | Capsules for oral administration (40 ug/kg) once daily for 24 weeks A4250 (odevixibat): A4250 is a small molecule and selective inhibitor of IBAT. | Capsules for oral administration (120 ug/kg) once daily for 24 weeks A4250 (odevixibat): A4250 is a small molecule and selective inhibitor of IBAT. | Capsules for oral administration (to match active) once daily for 24 weeks Placebo: Placebo identical in appearance to active drug (A4250). |
| Measure Participants | 23 | 19 | 20 |
| Least Squares Mean (Standard Error) [score on a scale] |
58.34
(8.580)
|
51.81
(9.459)
|
30.10
(9.119)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | A4250 Low Dose, Placebo |
|---|---|---|
| Comments | Analysis of the Proportion of Positive Pruritus Assessments at Participant Level over the 24-Week Treatment Period - Albireo ObsRO Instrument (AM and PM Scores) | |
| Type of Statistical Test | Superiority | |
| Comments | ANCOVA model including treatment, baseline pruritus score at AM and PM, PFIC type, and age category was used for treatment comparisons. A pooled analysis for the closed testing procedure was applied to control multiplicity. The one-sided adjusted p-value for an individual dose was calculated as the maximum value of the unadjusted p-value for the pooled analysis and the unadjusted p-value for the individual doses. One-sided adjusted p-value was reported. | |
| Statistical Test of Hypothesis | p-Value | 0.0019 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 28.23 | |
| Confidence Interval |
(2-Sided) 95% 9.83 to 46.64 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 9.182 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | A4250 High Dose, Placebo |
|---|---|---|
| Comments | Analysis of the Proportion of Positive Pruritus Assessments at Participant Level over the 24-Week Treatment Period - Albireo ObsRO Instrument (AM and PM Scores) | |
| Type of Statistical Test | Superiority | |
| Comments | ANCOVA model including treatment, baseline pruritus score at AM and PM, PFIC type, and age category was used for treatment comparisons. A pooled analysis for the closed testing procedure was applied to control multiplicity. The one-sided adjusted p-value for an individual dose was calculated as the maximum value of the unadjusted p-value for the pooled analysis and the unadjusted p-value for the individual doses. One-sided adjusted p-value was reported. | |
| Statistical Test of Hypothesis | p-Value | 0.0163 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 21.71 | |
| Confidence Interval |
(2-Sided) 95% 1.87 to 41.54 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 9.892 |
|
| Estimation Comments | ||
| Title | Percentage of Participants Experiencing at Least a 70% Reduction in Fasting s-BA Concentration From Baseline to the End of Treatment or Reaching a Level <= 70 μmol/L After 24 Weeks of Treatment (European Union and Rest of the World Primary Endpoint) |
|---|---|
| Description | Fasting s-BA baseline was calculated as the average of the last 2 values prior to the first dose. The end value was the average of the values at Weeks 22 and 24 after the start of double-blind treatment. Participants who had at least 70% reduction in Fasting s-BA from baseline to the end of treatment or reached <=70 μmol/L after 24 weeks of treatment were considered as responder. Participants with missing average at the end of treatment were classified as non-responder. Full analysis set was used for the analysis. |
| Time Frame | Over 24 weeks of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set (FAS) included all randomized participants who received at least 1 dose of study treatment. |
| Arm/Group Title | A4250 Low Dose | A4250 High Dose | Placebo |
|---|---|---|---|
| Arm/Group Description | Capsules for oral administration (40 ug/kg) once daily for 24 weeks A4250 (odevixibat): A4250 is a small molecule and selective inhibitor of IBAT. | Capsules for oral administration (120 ug/kg) once daily for 24 weeks A4250 (odevixibat): A4250 is a small molecule and selective inhibitor of IBAT. | Capsules for oral administration (to match active) once daily for 24 weeks Placebo: Placebo identical in appearance to active drug (A4250). |
| Measure Participants | 23 | 19 | 20 |
| Number of Responders |
10
43.5%
|
4
21.1%
|
0
0%
|
| Number of participants not meeting the responder definition |
13
56.5%
|
15
78.9%
|
20
100%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | A4250 Low Dose, Placebo |
|---|---|---|
| Comments | Analysis was based on the Cochran Mantel Haenszel test adjusting PFIC type. A pooled analysis for the closed testing procedure was applied to control multiplicity. The one-sided adjusted p-value for an individual dose was calculated as the maximum value of the unadjusted p-value for the pooled analysis and the unadjusted p-value for the individual doses. One-sided adjusted p-value was reported. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0015 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | proportion difference |
| Estimated Value | 0.435 | |
| Confidence Interval |
(2-Sided) 95% 0.2195 to 0.6551 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | A4250 High Dose, Placebo |
|---|---|---|
| Comments | Analysis was based on the Cochran Mantel Haenszel test adjusting PFIC type. A pooled analysis for the closed testing procedure was applied to control multiplicity. The one-sided adjusted p-value for an individual dose was calculated as the maximum value of the unadjusted p-value for the pooled analysis and the unadjusted p-value for the individual doses. One-sided adjusted p-value was reported. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0174 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | proportion difference |
| Estimated Value | 0.211 | |
| Confidence Interval |
(2-Sided) 95% 0.021 to 0.4557 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Adverse Events
| Time Frame | All serious and non-serious adverse events (AEs) were collected once the caregiver/participant had signed the informed consent form (ICF) and until the post-treatment follow-up (Visit 10) or 28 days after the last dose of study drug. | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Treatment emergent adverse events (TEAEs) were defined as any AE that occurred after 1st dose or AE occurred before 1st dose but worsened in severity on or after 1st dose. Treatment emergent serious adverse events and treatment emergent non-serious AEs are reported here. | |||||
| Arm/Group Title | A4250 Low Dose | A4250 High Dose | Placebo | |||
| Arm/Group Description | Capsules for oral administration (40 ug/kg) once daily for 24 weeks A4250 (odevixibat): A4250 is a small molecule and selective inhibitor of IBAT. | Capsules for oral administration (120 ug/kg) once daily for 24 weeks A4250 (odevixibat): A4250 is a small molecule and selective inhibitor of IBAT. | Capsules for oral administration (to match active) once daily for 24 weeks Placebo: Placebo identical in appearance to active drug (A4250). | |||
All Cause Mortality |
||||||
| A4250 Low Dose | A4250 High Dose | Placebo | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/23 (0%) | 0/19 (0%) | 0/20 (0%) | |||
Serious Adverse Events |
||||||
| A4250 Low Dose | A4250 High Dose | Placebo | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/23 (0%) | 3/19 (15.8%) | 5/20 (25%) | |||
| Cardiac disorders | ||||||
| Supraventricular tachycardia | 0/23 (0%) | 1/19 (5.3%) | 0/20 (0%) | |||
| General disorders | ||||||
| Pyrexia | 0/23 (0%) | 0/19 (0%) | 1/20 (5%) | |||
| Infections and infestations | ||||||
| Gastroenteritis adenovirus | 0/23 (0%) | 0/19 (0%) | 1/20 (5%) | |||
| H1N1 influenza | 0/23 (0%) | 0/19 (0%) | 1/20 (5%) | |||
| Influenza | 0/23 (0%) | 0/19 (0%) | 1/20 (5%) | |||
| Urinary tract infection | 0/23 (0%) | 1/19 (5.3%) | 1/20 (5%) | |||
| Viral infection | 0/23 (0%) | 0/19 (0%) | 1/20 (5%) | |||
| Viral upper respiratory tract infection | 0/23 (0%) | 0/19 (0%) | 1/20 (5%) | |||
| Injury, poisoning and procedural complications | ||||||
| Auricular haematoma | 0/23 (0%) | 0/19 (0%) | 1/20 (5%) | |||
| Investigations | ||||||
| Liver function test increased | 0/23 (0%) | 1/19 (5.3%) | 0/20 (0%) | |||
| Metabolism and nutrition disorders | ||||||
| Dehydration | 0/23 (0%) | 1/19 (5.3%) | 0/20 (0%) | |||
| Weight gain poor | 0/23 (0%) | 0/19 (0%) | 1/20 (5%) | |||
| Psychiatric disorders | ||||||
| Insomnia | 0/23 (0%) | 0/19 (0%) | 1/20 (5%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Neurodermatitis | 0/23 (0%) | 0/19 (0%) | 1/20 (5%) | |||
| Pruritus | 0/23 (0%) | 0/19 (0%) | 1/20 (5%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| A4250 Low Dose | A4250 High Dose | Placebo | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 19/23 (82.6%) | 16/19 (84.2%) | 17/20 (85%) | |||
| Blood and lymphatic system disorders | ||||||
| Iron deficiency anaemia | 0/23 (0%) | 0/19 (0%) | 1/20 (5%) | |||
| Splenomegaly | 0/23 (0%) | 2/19 (10.5%) | 0/20 (0%) | |||
| Ear and labyrinth disorders | ||||||
| Ear pain | 0/23 (0%) | 1/19 (5.3%) | 1/20 (5%) | |||
| Otorrhoea | 0/23 (0%) | 1/19 (5.3%) | 0/20 (0%) | |||
| Eye disorders | ||||||
| Eye discharge | 0/23 (0%) | 1/19 (5.3%) | 0/20 (0%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal discomfort | 0/23 (0%) | 1/19 (5.3%) | 0/20 (0%) | |||
| Abdominal pain | 2/23 (8.7%) | 1/19 (5.3%) | 0/20 (0%) | |||
| Abdominal pain upper | 1/23 (4.3%) | 1/19 (5.3%) | 0/20 (0%) | |||
| Constipation | 0/23 (0%) | 0/19 (0%) | 4/20 (20%) | |||
| Dental caries | 0/23 (0%) | 1/19 (5.3%) | 0/20 (0%) | |||
| Diarrhoea | 9/23 (39.1%) | 4/19 (21.1%) | 1/20 (5%) | |||
| Frequent bowel movements | 0/23 (0%) | 0/19 (0%) | 1/20 (5%) | |||
| Gastrooesophageal reflux disease | 1/23 (4.3%) | 0/19 (0%) | 0/20 (0%) | |||
| Mouth ulceration | 0/23 (0%) | 1/19 (5.3%) | 0/20 (0%) | |||
| Toothache | 0/23 (0%) | 0/19 (0%) | 1/20 (5%) | |||
| Vomiting | 4/23 (17.4%) | 3/19 (15.8%) | 0/20 (0%) | |||
| General disorders | ||||||
| Influenza like illness | 1/23 (4.3%) | 0/19 (0%) | 0/20 (0%) | |||
| Injection site swelling | 1/23 (4.3%) | 0/19 (0%) | 0/20 (0%) | |||
| Pyrexia | 7/23 (30.4%) | 5/19 (26.3%) | 5/20 (25%) | |||
| Hepatobiliary disorders | ||||||
| Cholelithiasis | 0/23 (0%) | 1/19 (5.3%) | 0/20 (0%) | |||
| Hepatomegaly | 0/23 (0%) | 1/19 (5.3%) | 0/20 (0%) | |||
| Jaundice | 1/23 (4.3%) | 0/19 (0%) | 0/20 (0%) | |||
| Infections and infestations | ||||||
| Adenovirus infection | 0/23 (0%) | 0/19 (0%) | 1/20 (5%) | |||
| Bronchitis | 1/23 (4.3%) | 0/19 (0%) | 0/20 (0%) | |||
| Conjunctivitis | 1/23 (4.3%) | 0/19 (0%) | 0/20 (0%) | |||
| Ear infection | 1/23 (4.3%) | 0/19 (0%) | 0/20 (0%) | |||
| Gastroenteritis | 1/23 (4.3%) | 0/19 (0%) | 0/20 (0%) | |||
| Gastroenteritis norovirus | 0/23 (0%) | 1/19 (5.3%) | 0/20 (0%) | |||
| Gastroenteritis viral | 1/23 (4.3%) | 0/19 (0%) | 1/20 (5%) | |||
| H1N1 influenza | 0/23 (0%) | 0/19 (0%) | 1/20 (5%) | |||
| Hand-foot-and-mouth disease | 0/23 (0%) | 0/19 (0%) | 1/20 (5%) | |||
| Influenza | 0/23 (0%) | 1/19 (5.3%) | 1/20 (5%) | |||
| Klebsiella infection | 1/23 (4.3%) | 0/19 (0%) | 0/20 (0%) | |||
| Nasopharyngitis | 1/23 (4.3%) | 2/19 (10.5%) | 1/20 (5%) | |||
| Otitis media | 0/23 (0%) | 2/19 (10.5%) | 0/20 (0%) | |||
| Parotitis | 0/23 (0%) | 1/19 (5.3%) | 0/20 (0%) | |||
| Post procedural infection | 1/23 (4.3%) | 0/19 (0%) | 0/20 (0%) | |||
| Respiratory tract infection | 0/23 (0%) | 1/19 (5.3%) | 0/20 (0%) | |||
| Urinary tract infection | 1/23 (4.3%) | 0/19 (0%) | 2/20 (10%) | |||
| Viral diarrhoea | 1/23 (4.3%) | 0/19 (0%) | 0/20 (0%) | |||
| Viral infection | 0/23 (0%) | 1/19 (5.3%) | 1/20 (5%) | |||
| Viral rash | 0/23 (0%) | 0/19 (0%) | 1/20 (5%) | |||
| Viral upper respiratory tract infection | 2/23 (8.7%) | 0/19 (0%) | 0/20 (0%) | |||
| Rhinitis | 2/23 (8.7%) | 0/19 (0%) | 0/20 (0%) | |||
| Sinusitis bacterial | 0/23 (0%) | 1/19 (5.3%) | 0/20 (0%) | |||
| Skin candida | 0/23 (0%) | 0/19 (0%) | 1/20 (5%) | |||
| Tonsillitis | 0/23 (0%) | 0/19 (0%) | 1/20 (5%) | |||
| Upper respiratory tract infection | 3/23 (13%) | 5/19 (26.3%) | 3/20 (15%) | |||
| Injury, poisoning and procedural complications | ||||||
| Auricular haematoma | 0/23 (0%) | 0/19 (0%) | 1/20 (5%) | |||
| Scar | 0/23 (0%) | 0/19 (0%) | 1/20 (5%) | |||
| Scratch | 1/23 (4.3%) | 0/19 (0%) | 2/20 (10%) | |||
| Skin abrasion | 0/23 (0%) | 0/19 (0%) | 1/20 (5%) | |||
| Tibia fracture | 1/23 (4.3%) | 0/19 (0%) | 0/20 (0%) | |||
| Investigations | ||||||
| Alanine aminotransferase increased | 3/23 (13%) | 3/19 (15.8%) | 1/20 (5%) | |||
| Aspartate aminotransferase increased | 2/23 (8.7%) | 1/19 (5.3%) | 1/20 (5%) | |||
| Bilirubin conjugated increased | 1/23 (4.3%) | 0/19 (0%) | 0/20 (0%) | |||
| Blood alkaline phosphatase increased | 1/23 (4.3%) | 2/19 (10.5%) | 1/20 (5%) | |||
| Blood bilirubin increased | 3/23 (13%) | 2/19 (10.5%) | 2/20 (10%) | |||
| Blood creatine phosphokinase increased | 0/23 (0%) | 1/19 (5.3%) | 2/20 (10%) | |||
| Blood creatinine decreased | 1/23 (4.3%) | 0/19 (0%) | 0/20 (0%) | |||
| Blood creatinine increased | 0/23 (0%) | 0/19 (0%) | 1/20 (5%) | |||
| International normalised ratio increased | 1/23 (4.3%) | 0/19 (0%) | 1/20 (5%) | |||
| Liver palpable | 1/23 (4.3%) | 0/19 (0%) | 0/20 (0%) | |||
| Platelet count increased | 0/23 (0%) | 1/19 (5.3%) | 1/20 (5%) | |||
| Product residue present | 1/23 (4.3%) | 0/19 (0%) | 0/20 (0%) | |||
| Vitamin D decreased | 0/23 (0%) | 1/19 (5.3%) | 0/20 (0%) | |||
| Vitamin E increased | 1/23 (4.3%) | 0/19 (0%) | 0/20 (0%) | |||
| Weight decreased | 1/23 (4.3%) | 0/19 (0%) | 0/20 (0%) | |||
| White blood cell count increased | 0/23 (0%) | 0/19 (0%) | 2/20 (10%) | |||
| Metabolism and nutrition disorders | ||||||
| Hypocalcaemia | 0/23 (0%) | 0/19 (0%) | 1/20 (5%) | |||
| Hypophosphataemia | 0/23 (0%) | 0/19 (0%) | 1/20 (5%) | |||
| Vitamin A deficiency | 0/23 (0%) | 1/19 (5.3%) | 0/20 (0%) | |||
| Vitamin D deficiency | 0/23 (0%) | 2/19 (10.5%) | 1/20 (5%) | |||
| Vitamin E deficiency | 0/23 (0%) | 1/19 (5.3%) | 0/20 (0%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Neck mass | 0/23 (0%) | 0/19 (0%) | 1/20 (5%) | |||
| Nervous system disorders | ||||||
| Dizziness | 0/23 (0%) | 1/19 (5.3%) | 0/20 (0%) | |||
| Headache | 0/23 (0%) | 1/19 (5.3%) | 1/20 (5%) | |||
| Psychiatric disorders | ||||||
| Irritability | 0/23 (0%) | 1/19 (5.3%) | 1/20 (5%) | |||
| Selective eating disorder | 0/23 (0%) | 0/19 (0%) | 1/20 (5%) | |||
| Renal and urinary disorders | ||||||
| Chromaturia | 1/23 (4.3%) | 0/19 (0%) | 0/20 (0%) | |||
| Cystitis haemorrhagic | 0/23 (0%) | 1/19 (5.3%) | 0/20 (0%) | |||
| Haematuria | 1/23 (4.3%) | 0/19 (0%) | 0/20 (0%) | |||
| Reproductive system and breast disorders | ||||||
| Genital rash | 0/23 (0%) | 1/19 (5.3%) | 0/20 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 0/23 (0%) | 2/19 (10.5%) | 3/20 (15%) | |||
| Epistaxis | 1/23 (4.3%) | 1/19 (5.3%) | 1/20 (5%) | |||
| Nasal obstruction | 1/23 (4.3%) | 0/19 (0%) | 0/20 (0%) | |||
| Oropharyngeal pain | 0/23 (0%) | 0/19 (0%) | 1/20 (5%) | |||
| Rhinitis allergic | 0/23 (0%) | 1/19 (5.3%) | 0/20 (0%) | |||
| Rhinorrhoea | 1/23 (4.3%) | 0/19 (0%) | 0/20 (0%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Dermatitis allergic | 0/23 (0%) | 1/19 (5.3%) | 0/20 (0%) | |||
| Dermatitis diaper | 0/23 (0%) | 0/19 (0%) | 1/20 (5%) | |||
| Nail discolouration | 0/23 (0%) | 0/19 (0%) | 1/20 (5%) | |||
| Neurodermatitis | 0/23 (0%) | 0/19 (0%) | 1/20 (5%) | |||
| Pruritus | 2/23 (8.7%) | 1/19 (5.3%) | 0/20 (0%) | |||
| Rash | 0/23 (0%) | 0/19 (0%) | 3/20 (15%) | |||
| Rash vesicular | 1/23 (4.3%) | 0/19 (0%) | 0/20 (0%) | |||
| Surgical and medical procedures | ||||||
| Cardiac ablation | 0/23 (0%) | 1/19 (5.3%) | 0/20 (0%) | |||
| Vascular disorders | ||||||
| Hypertension | 0/23 (0%) | 0/19 (0%) | 1/20 (5%) | |||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Albireo will retain the ownership of all data. All proposed publications based on this study must be subject to the sponsor's approval requirements.
Results Point of Contact
| Name/Title | Patrick Horn, MD, PhD |
|---|---|
| Organization | Albireo AB |
| Phone | +1 (857) 378- 2035 |
| medinfo@albireopharma.com |
Responsible Party:
Albireo
ClinicalTrials.gov Identifier:
NCT03566238
Other Study ID Numbers:
- A4250-005
First Posted:
Jun 25, 2018
Last Update Posted:
Sep 5, 2021
Last Verified:
Aug 1, 2021