Clinical Trials Register

Summary
EudraCT Number:	2013-002924-17
Sponsor's Protocol Code Number:	A3384-001
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2013-12-03
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2013-002924-17

A.3

Full title of the trial

A double-blind, randomized, placebo-controlled, study to demonstrate the efficacy and safety of 250 mg or 1 g A3384 administered orally twice daily for two weeks to patients with Bile Acid Malabsorption (BAM)/Bile Acid Diarrhoea (BAD)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A.3.2

Name or abbreviated title of the trial where available

A3384 in BAM/BAD

A.4.1

Sponsor's protocol code number

A3384-001

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Albireo AB
B.1.3.4	Country	Sweden
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Albireo AB
B.4.2	Country	Sweden
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Albireo AB
B.5.2	Functional name of contact point	Responsible Medical Officer
B.5.3	Address:
B.5.3.1	Street Address	Arvid Wallgrens Backe 20
B.5.3.2	Town/ city	Gothenburg
B.5.3.3	Post code	413 46
B.5.3.4	Country	Sweden
B.5.4	Telephone number	+46 31 741 1480
B.5.6	E-mail	hans.graffner@albireopharma.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.2	Product code	A3384
D.3.4	Pharmaceutical form	Capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CHOLESTYRAMINE
D.3.9.1	CAS number	9007-26-5
D.3.9.2	Current sponsor code	A3384
D.3.9.4	EV Substance Code	AS1
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	250
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Patients with Bile Acid Malabsorption (BAM)/Bile Acid Diarrhoea (BAD)

E.1.1.1

Medical condition in easily understood language

The patients have a disturbed uptake (reabsorption) of bile acids in the small intestine. This leading to bile acids reaches the colon. Which then leads to symptoms like diarrhoea.

E.1.1.2

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary efficacy objective of this study is to demonstrate the efficacy of twice daily oral doses of 250 mg or 1 g A3384 during a two week treatment period in patients with BAM, as determined by the # of bowel movements (BMs).
The primary safety objective of this study is to assess the safety and tolerability of twice daily oral doses of 250 mg or 1 g A3384 during a two week treatment period in patients with BAM, as determined by the occurrence of treatment-emergent SAEs.

E.2.2

Secondary objectives of the trial

Secondary efficacy objectives of this study are to demonstrate the efficacy of twice daily oral doses of 250 mg or 1 g A3384 during a two week treatment period on other BM parameters and BAM symptoms.

Secondary safety objectives of this study include assessment of the safety and tolerability of twice daily oral doses of 250 mg or 1 g A3384 during a two week treatment period, as determined by the occurrence of treatment-emergent AEs and changes in other safety parameters including laboratory tests and vital signs.

Exploratory efficacy objectives of this study include assessments of serum concentrations of BAs and assessments of pharmacodynamic parameters of bile acid modulation such as C4 and FGF19.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Symptoms compatible with the diagnosis of Bile Acid Malabsorption/Bile Acid Diarrhoea (BAM/BAD) with onset >12 months prior to randomization;
o SeHCAT 7 day retention of less than 10% with measurement conducted within the last 36 months and no dramatic change in symptomatology since the SeHCAT assessment
o A history of at least 3 liquid or soft stools ( BSFS ≥5) per day on average calculated from 7 days without therapy
o The last seven days before randomization having had >21 BMs of which >50% should be BSFS ≥5 (Evaluated pre-randomization at Visit 3)
• The patient reports having understood and has signed both the ICF and is willing to comply with all study visits and assessments;
• The patient is a male or non-pregnant female ≥18 years of age and ≤80 years of age with body mass index (BMI) ≥18.5 but <35;
• Having had a macroscopically normal colonoscopy with no histological signs of microscopic colitis within 5 years of screening.

E.4

Principal exclusion criteria

• Any condition that, in the opinion of the Investigator constitutes a risk for the patient or a contraindication for participation and completion of the study, or could interfere with study objectives, conduct, or evaluations.
• An identified cause for BAM such as surgical intestinal resection or bypass, IBD or drug use
• Patients with other diagnoses leading to diarrhoea, including colorectal neoplasia, ulcerative colitis, coeliac disease, chronic pancreatitis or drug-induced diarrhoea.
• The patient has a structural abnormality of the GI tract or a disease or condition that can affect GI motility.
• The patient has a known, active, clinically significant acute or chronic infection, or any major episode of infection requiring hospitalization or treatment with parenteral anti infectives within 4 weeks of treatment start (study day 1) or completion of oral anti-infective treatment within 2 weeks prior to start of screening period;
• The patient has unexplained and clinically significant GI alarm signals (e.g., lower GI bleeding or hem-positive stool, iron-deficiency anaemia, unexplained weight loss) or systemic signs of infection or colitis.
• The patient has rectal bleeding and/or is hem-positive in the absence of known internal or external haemorrhoids.
• The patient has a history of cancer with last date of proven disease activity/presence of malignancy within 5 years, except for adequately treated basal cell carcinoma of the skin, cervical dysplasia, or carcinoma in situ of the skin or the cervix.
• Previous biliary surgery, excluding cholecystectomy.
• Other reason for diarrhoea such as pancreatitis, celiac disease, infection etc.
• Treatment with bile acid sequestrants (cholestyramine, colesevelam, colestipol or similar) after Baseline period 2 and before Visit 4.
• Treatment with loperamide or codeine after Visit 1 and before Visit 4.
• The patient has laboratory test levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) or alkaline phosphatase (AP) >2.5 x the upper limit of normal (ULN) or total bilirubin >1.5 x ULN
• Chronic liver or chronic kidney disease
• Active, serious medical disease with life expectancy less than 5 years
• Active substance abuse in the year before Screening
• Allergy to cholestyramine
• The patient has a history of a psychiatric disorder requiring hospitalization or suicide attempt in the 2 years prior to study inclusion;
• The patient has participated in any investigational clinical study within 30 days prior to Screening or within 5 half-lives of the investigated compound (whichever is longer) prior to Screening Baseline (unless the patient was never randomized to study treatment), or plans to participate in another clinical study during this study;
• The patient is a pregnant, breast-feeding or lactating female.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint is change from Baseline in number of BMs during the second treatment week (last 7 days of reporting).

E.5.1.1

Timepoint(s) of evaluation of this end point

The primary baseline period is defined as the last 7 days assessments recorded during Baseline period 2, prior to the first administration of study drug (Day 1).
Timeponts of treatment is second treatment week (or last 7 days of reporting)

E.5.2

Secondary end point(s)

Secondary efficacy endpoints are:
• Change from Baseline in average severity of diarrhoea during the second treatment week (last 7 days of reporting).
• Change from Baseline in average severity of abdominal discomfort during the second treatment week (last 7 days of reporting).
• Change from Baseline in average severity of abdominal bloating during the second treatment week (last 7 days of reporting).
• Change from Baseline in average BSFS during the second treatment week (last 7 days of reporting).

Explorative endpoints are:
• Change from Baseline 2 in FGF19 at Visit 4 and Visit 5
• Change from Baseline 1 in FGF19 at Visit 4
• Change from Baseline 2 in C4 at Visit 4 and Visit 5
• Change from Baseline 1 in C4 at Visit 4
• Change from Baseline 2 in total s-BA at Visit 4 and Visit 5
• Change from Baseline 1 in total s-BA at Visit 4

E.5.2.1

Timepoint(s) of evaluation of this end point

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1