Clinical Trials Register

Summary
EudraCT Number:	2016-002416-41
Sponsor's Protocol Code Number:	201000
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2017-09-05
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

Poland - Office for Medicinal Products

A.2

EudraCT number

2016-002416-41

A.3

Full title of the trial

A randomized, double-blind, multi-dose, placebo-controlled study to evaluate the efficacy, safety and tolerability of GSK2330672 administration for the treatment of pruritus in patients with primary biliary cholangitis.
(GLIMMER: GSK2330672 triaL of Ibat inhibition with Multidose Measurement for Evaluation of Response).

A.3.1

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

Dose response study of GSK2330672 for the treatment of pruritus in patients with primary biliary cholangitis – The GLIMMER Study

A.4.1

Sponsor's protocol code number

201000

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	GlaxoSmithKline Research & Development Ltd
B.1.3.4	Country	United Kingdom
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	GSK R&D
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	GlaxoSmithKline Research and Development Ltd
B.5.2	Functional name of contact point	GSK Clinical Support Help Desk
B.5.3	Address:
B.5.3.1	Street Address	Iron Bridge Road, Stockley Park West
B.5.3.2	Town/ city	Uxbridge, Middlesex
B.5.3.3	Post code	UB11 1BU
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+44 0208 990 44 66
B.5.6	E-mail	GSKClinicalSupportHD@gsk.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.3.1	Product name	GSK2330672
D.3.2	Product code	GSK2330672
D.3.4	Pharmaceutical form	Tablet
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	GSK2330672
D.3.9.1	CAS number	1345983-37-0
D.3.9.2	Current sponsor code	GSK2330672
D.3.9.3	Other descriptive name	GSK2330672
D.3.9.4	EV Substance Code	SUB121295
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	10
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.IMP: 2
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.3.1	Product name	GSK2330672
D.3.2	Product code	GSK2330672
D.3.4	Pharmaceutical form	Tablet
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	GSK2330672
D.3.9.1	CAS number	1345983-37-0
D.3.9.2	Current sponsor code	GSK2330672
D.3.9.3	Other descriptive name	GSK2330672
D.3.9.4	EV Substance Code	SUB121295
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	45
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	Tablet
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

Primary biliary cholangitis (PBC)

E.1.1.1

Medical condition in easily understood language

Itch due to primary biliary cholangitis (PBC).

E.1.1.2

Therapeutic area

Body processes [G] - Metabolic Phenomena [G03]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10008604
E.1.2	Term	Cholangitis
E.1.2	System Organ Class	10019805 - Hepatobiliary disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10037087
E.1.2	Term	Pruritus
E.1.2	System Organ Class	10040785 - Skin and subcutaneous tissue disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

● To investigate the dose response of oral GSK2330672 on itch in PBC patients with moderate to severe pruritus at Baseline.

E.2.2

Secondary objectives of the trial

Key Secondary Objectives:
● To characterize the effects of GSK2330672 compared to placebo on impact of symptoms and quality of life in PBC patients with moderate to severe pruritus at Baseline.
●To evaluate the effects of GSK2330672 compared to placebo on markers of disease among participants at high risk of PBC progression (i.e., those with serum ALP concentrations <1.67xULN and/or total bilirubin concentrations >ULN at Day 1).
(Please refer to study protocol 201000 for other Secondary Objectives)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Participants are eligible to be included in the study only if all of the following criteria apply:
Age
1. Participant must be 18 to 80 years of age inclusive, at the time of signing the informed consent.
Type of Participant and Disease Characteristics
2. Participants who have proven PBC, as demonstrated by having at least 2 of the following:
• History of sustained increased ALP levels >upper limit of normal (ULN) first recognized at least 6 months prior to the Screening Visit (Note: Sustained ALP elevations at the time of Screening is not required, recognizing that the ALP may have decreased after institution of UDCA therapy as described in inclusion number 4).
• Documented positive anti-mitochondrial antibody (AMA) titer (>1:40 titer on immunofluorescence or M2 positive by ELISA) or PBC-specific antinuclear antibodies (antinuclear dot and /or nuclear rim positive).
• Liver biopsy (at any time in the past) consistent with PBC.
3. Participants must rate their itch severity as being ≥4 on a 0 to 10 point scale for the majority of time (at least half the days, as recalled by the participant) during the 8 weeks prior to the Screening Visit. Periods of low itch or no itch are acceptable as long as the worst daily itch score is ≥4 on the majority of days.
4. Participants who are currently taking UDCA should be on stable doses of UDCA for >8 weeks at time of screening. Participants not taking UDCA due to intolerance may be enrolled 8 weeks after their last dose of UDCA.
Note: no changes or discontinuation is permitted until completion of the Main Study Period.
Sex
5. Male and/or female:
a. Female participants:
A female participant is eligible to participate if she is not pregnant (see Appendix 2 of study protocol), not breastfeeding, and at least one of the following conditions applies:
(i) Not a woman of childbearing potential (WOCBP) as defined in Appendix 2 of study protocol
OR
(ii) A WOCBP who agrees to follow the contraceptive guidance in Appendix 2 of study protocol during the treatment period and until at least 4 weeks after the last dose of study treatment.
Informed Consent
6. Capable of giving signed informed consent as described in Appendix 3 of study protocol which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.

E.4

Principal exclusion criteria

Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
1. Screening total bilirubin >2x ULN. Isolated bilirubin >2x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%.
2. Screening ALT or aspartate aminotransferase (AST) >6x ULN.
3. Screening estimated glomerular filtration rate (eGFR) <45 mL/min/1.73m² based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
4. History or presence of hepatic decompensation (e.g., variceal bleeds, encephalopathy or ascites).
5. Presence of actively replicating viral hepatitis B or C (HBV, HCV) infection and/or confirmed hepatocellular carcinoma or biliary cancer. Note: Other hepatic conditions (e.g., primary sclerosing cholangitis (PSC), alcoholic liver disease, autoimmune hepatitis, non-alcoholic steatohepatitis [NASH] are permitted if PBC is the dominant liver injury in the investigator's opinion
6. Current diarrhea
7. Current symptomatic cholelithiasis or inflammatory gall bladder disease. Participants with history of cholecystectomy ≥3 months before screening may be eligible for enrollment.
8. Any current medical condition (e.g. psychiatric disorder, senility or dementia), which may affect the participant’s ability to comply with the protocol specified procedures.
Prior/Concomitant Therapy
9. Initiation or increase in dose of colchicine, methotrexate, azathioprine, or systemic corticosteroids in the 2 months prior to screening.
Note: If a change in dose in any of these medications is anticipated during the course of the study, the participant should be excluded. [Rationale: Limited evidence indicates these drugs may alter disease progression in some PBC patients.]
10. Initiation or increase in dose of bezafibrate or fenofibrate at any time during the 3 months prior to screening. Participants may join the study on stable doses of these medications, but no change or discontinuation is permitted until completion of the Main Study Period.
11. Initiation or increase in dose of any of the following in the 8 weeks prior to screening: rifampicin, naltrexone, naloxone, nalfurafine, or sertraline. Participants may join the study on stable or decreased doses of these medications, but no change in dose is permitted until completion of the Main Study Period.
12. Bile acid binding resin use: a participant must discontinue use of cholestyramine, colesevelam, colestipol or colestimide prior to the start of the Initial Study Period (no later than Day -2). Note: these drugs may be administered after completion of the Main Study Period, if clinically indicated.
13. Obeticholic acid use: a participant must discontinue use of obeticholic acid at least 8 weeks prior to the start of the Initial Study Period and may not restart until after the end of the study.
14. Administration of any other IBAT inhibitor in the 3 months prior to Screening [Rationale: Effects of another IBAT inhibitor may influence pruritus.]
Prior/Concurrent Clinical Study Experience
15. Current enrollment or participation within the 8 weeks before start of the Initial Study Period, in any other clinical study involving an investigational study treatment.
Diagnostic assessments
16. QTc >480 msec
NOTES:
-The QTc is the QT interval corrected for heart rate according to Bazett's formula (QTcB), Fridericia's formula (QTcF), and/or another method. It is either machine-read or manually over-read.
-The specific formula used to determine eligibility and discontinuation for an individual participant should be determined prior to initiation of the study. In other words, several different formulas cannot be used to calculate the QTc for an individual participant and then the lowest QTc value used to include or discontinue the participant from the trial.
17. History of sensitivity to the study treatment or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation in the study.
18. History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (~240 mL) of beer, 1 glass (125 mL) of wine or 1 measure (25 mL) of spirits.

E.5 End points

E.5.1

Primary end point(s)

Mean change from Baseline at Week 16 in the Mean Worst Daily Itch Score.

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 16

E.5.2

Secondary end point(s)

● Mean change from Baseline at Week 16 in PBC-40 Scale.
In participants meeting the criteria for high risk of PBC progression:
● Mean change from Baseline at Week 16 in serum ALP concentrations.
● Proportion of participants having serum ALP concentrations <1.67x ULN and total bilirubin concentrations ≤ULN at Week 16.
● Mean change from Baseline at Week 16 in serum ALT, AST, GGT, total bilirubin and albumin concentrations and PT/INR.

E.5.2.1

Timepoint(s) of evaluation of this end point

Week 16

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

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

Yes

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

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

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

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Canada

France

Japan

Netherlands

Spain

United Kingdom

United States

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.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

130

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

150

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

The Sponsor will not provide treatment after the end of the study; participants should be managed according to their treating physician.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2017-11-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-09-18

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2020-04-16

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