Clinical Trials Register

Summary
EudraCT Number:	2013-004195-36
Sponsor's Protocol Code Number:	120542
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:	2014-06-04
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

2013-004195-36

A.3

Full title of the trial

A randomised, double-blind, placebo-controlled, phase II clinical trial with a cross-over design assessing efficacy of a single dose of bumetamide in reducing focal attack severity in hypokalaemic periodic paralysis assessed using the McManis protocol.

A.3.1

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

Bumetanide in Hypokalaemic Periodic Paralysis

A.3.2

Name or abbreviated title of the trial where available

Bumetanide in Hypokalaemic Periodic Paralysis

A.4.1

Sponsor's protocol code number

120542

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	University College of London
B.1.3.4	Country	United Kingdom
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	MRC Centre for Neuromuscular Diseases
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	University College London - Joint Research Office
B.5.2	Functional name of contact point	Sponsor Regulatory Advisor
B.5.3	Address:
B.5.3.1	Street Address	UCL, Gower Street
B.5.3.2	Town/ city	London
B.5.3.3	Post code	WC1E 6BT
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	02076796469
B.5.5	Fax number	02031082312
B.5.6	E-mail	a.akinyemi@ucl.ac.uk

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	Yes
D.2.1.1.1	Trade name	Bumetanide
D.2.1.1.2	Name of the Marketing Authorisation holder	Teva UK Limited
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	2mg Overencapsulated Bumetanide
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	Bumetanide
D.3.9.1	CAS number	28395-03-1
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	2
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

Hypokalaemic Periodic Paralysis

E.1.1.1

Medical condition in easily understood language

Attacks of muscle weakness associated with low potassium levels in the blood.

E.1.1.2

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.0
E.1.2	Level	PT
E.1.2	Classification code	10016208
E.1.2	Term	Familial periodic paralysis
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess the efficacy of bumetanide in reducing the severity of a focal attack of muscle weakness affecting a small hand muscle one hour after attack onset in hypokalaemic periodic paralysis.

E.2.2

Secondary objectives of the trial

1) To assess the efficacy of bumetanide in reducing the duration of a focal attack;
2) To assess the efficacy of bumetanide in reducing the severity of a focal attack early (0-2hr) after treatment administration;
3) To assess the efficacy of bumetanide in reducing the severity of a focal attack late (2-4hr) after treatment administration;
4) To assess the safety of bumetanide in hypokalaemic periodic paralysis;

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1) At least 18 years of age;
2) Diagnosis of genetically confirmed HypoPP;
3) Clinical symptoms or signs of active symptomatic disease (at least 1 attack in last 12 months);
4) Practicing an acceptable method of birth control for the duration of the trial. Methods of birth control for women and men are addressed on Patient Information Sheet and on section section 11.4.5 of this protocol;

E.4

Principal exclusion criteria

1) Inability or unwillingness to provide informed consent;
2) People older than 64 years old;
3) Other conditions causing non-dominant hand weakness which could interfere with study measurements (e.g. due to a stroke, trauma or arthritis);
4) Patients with a history of cardiac disease, renal failure or hepatic disease. Note: abnormalities in serum transaminases are common in people with HypoPP as they arise from skeletal muscle rather than any specific liver abnormality. Consequently, raised serum bilirubin >20% above the baseline value will be used to identify abnormal liver function;
5) Women who are pregnant or breast-feeding;
6) Patients with a previous history of diabetes, porphyria, symptomatic hypotension, prostatic hypertrophy or difficulty with micturition, or allergy to sulfonamides or thiazides;
7) Patients on lithium;
8) Patients known to be allergic to bumetanide or its excipients;
9) Patients with a history of inadequately treated Addison's disease;
10) Patients participating in another interventional trial in the previous 1 month.

E.5 End points

E.5.1

Primary end point(s)

The primary outcome measure is focal attack severity one hour after treatment administration. Treatment will be administered when the CMAP amplitude reaches 60% of its peak value.

E.5.1.1

Timepoint(s) of evaluation of this end point

This will be measured as CMAP amplitude expressed as a percent of peak CMAP during or after the McManis exercise 1 hour after treatment administration.

E.5.2

Secondary end point(s)

1)To assess the efficacy of bumetanide in reducing the duration of a localised attack;
2)To assess the efficacy of bumetanide in reducing the severity of a focal attack early (0-2hr) after treatment administration;
3)To assess the efficacy of bumetanide in reducing the severity of a focal attack late (2-4hr) after treatment administration;
4)To assess the safety of bumetanide in hypokalaemic periodic paralysis;

E.5.2.1

Timepoint(s) of evaluation of this end point

o The effect of treatment on focal attack duration. This will be measured as the time between treatment administration until CMAP returns to 65% peak CMAP.
o The initial effect of treatment on severity of a focal attack within the first two hours. This will be measured as CMAP amplitude (in percent of peak) area under the curve (AUC) from treatment administration until two hours post-treatment.
o The late effect of treatment on severity of a focal attack two to four hours post treatment. This will be measured as CMAP amplitude (in percent of peak) AUC from two hours until four hours post-treatment.
o Safety of bumetanide to include self-reported side effects and changes of serum potassium.

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

E.6.7

Pharmacodynamic

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

E.8.1.6

Cross over

Yes

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

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

The end of the trial will be the date of the last follow up telephone call.

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