Clinical Trials Register

Summary
EudraCT Number:	2012-005761-12
Sponsor's Protocol Code Number:	SPD426-406
National Competent Authority:	Slovakia - SIDC (Slovak)
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-03-28
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

Slovakia - SIDC (Slovak)

A.2

EudraCT number

2012-005761-12

A.3

Full title of the trial

A Phase 4, Randomized, Double-blind, Placebo-controlled, Crossover Study to Investigate the Clinical Benefit of Midodrine Hydrochloride in Male and Female Subjects with Symptomatic Orthostatic Hypotension

Randomizovaná dvojito zaslepená placebom kontrolovaná štúdia so skríženým dizajnom 4. fázy na zisťovanie klinického prínosu midodrínhydrochloridu u mužov a žien so symptomatickou ortostatickou hypotenziou

A.3.1

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

A study to assess the clinical benefit of Midodrine Hydrochloride in patients with symptomatic orthostatic hypotension.

Štúdia na zisťovanie klinického prínosu midodrínhydrochloridu u pacientov so symptomatickou ortostatickou hypotenziou

A.4.1

Sponsor's protocol code number

SPD426-406

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	Shire Development LLC
B.1.3.4	Country	United States
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	Shire Development LLC
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Shire Pharmaceuticals Limited
B.5.2	Functional name of contact point	Medical Communications
B.5.3	Address:
B.5.3.1	Street Address	Hampshire International Business Park
B.5.3.2	Town/ city	Chineham, Basingstoke
B.5.3.3	Post code	RG24 8EP
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	448000556614
B.5.5	Fax number	4401256894714
B.5.6	E-mail	medinfoglobal@shire.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	Yes
D.2.1.1.1	Trade name	Midodrine Hydrochloride
D.2.1.1.2	Name of the Marketing Authorisation holder	Upsher Smith Laboratories
D.2.1.2	Country which granted the Marketing Authorisation	United States
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	Midodrine
D.3.2	Product code	SPD426
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	MIDODRINE HYDROCHLORIDE
D.3.9.1	CAS number	3092-17-9
D.3.9.2	Current sponsor code	SPD426
D.3.9.4	EV Substance Code	SUB03291MIG
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	2.5
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	Yes
D.2.1.1.1	Trade name	Midodrine Hydrochloride
D.2.1.1.2	Name of the Marketing Authorisation holder	Upsher Smith Laboratories
D.2.1.2	Country which granted the Marketing Authorisation	United States
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	Midodrine
D.3.2	Product code	SPD426
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	MIDODRINE HYDROCHLORIDE
D.3.9.1	CAS number	3092-17-9
D.3.9.2	Current sponsor code	SPD426
D.3.9.4	EV Substance Code	SUB03291MIG
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	2.5
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

Symptomatic orthostatic hypotension (SOH)

E.1.1.1

Medical condition in easily understood language

A significant decrease in blood pressure on standing or stretching that may cause fainting, dizziness or lightheadedness, unsteadiness, and blurred or impaired vision, among other symptoms.

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	15.1
E.1.2	Level	LLT
E.1.2	Classification code	10021102
E.1.2	Term	Hypotension orthostatic symptomatic
E.1.2	System Organ Class	100000004866

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 assess the clinical benefit of midodrine HCl in subjects with SOH in a crossover design study by measuring the time to onset of syncopal symptoms/near syncope (of sufficient severity that would cause the subject to ask that the tilt table be returned to the horizontal position) during a protocolized tilt table test

E.2.2

Secondary objectives of the trial

To assess the safety of midodrine HCl after single dose administration

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male and female subjects must be 18 years of age or older and ambulatory (when receiving adequate therapy for their SOH).

2. Females of child-bearing potential (FOCP) must have a negative serum beta human chorionic gonadotropin (HCG) pregnancy test. These females should abstain from sexual activity that could result in a pregnancy, or agree to use acceptable contraceptives throughout the period of the entire study and for 30 days after the last dose of investigational product.

3. A documented history of severe SOH (eg, due to Parkinson’s disease, Shy-Drager syndrome, multiple system atrophy, pure autonomic failure, or autonomic neuropathies) that, in the judgment of the treating physician, has required treatment with midodrine HCl, and has been at a stable dose for at least 3 months.

4. The subject has manifested at least 1 of the following symptoms while standing or had a medical history of 1 of the following when not treated for orthostatic hypotension (OH): dizziness, lightheadedness, feeling faint, or feeling like they might black out.

5. The subject is willing and able to undergo the procedures required by the protocol, including inpatient stay as required, assessment completion, protocol compliance, and participation in the placebo dosing period(s).

6. The subject has adequate hydration status (as assessed by physical examination and clinical laboratory parameters, eg, urine specific gravity).

7. Ability to provide written, signed, and dated informed consent to participate in the study

E.4

Principal exclusion criteria

1. The subject is a pregnant or lactating female.

2. The subject has pre-existing sustained supine hypertension greater than 180mmHg systolic and 110mmHg diastolic BP or had these measurements at the Screening Visit. Sustained is defined as persistently greater at 2 separate measurements at least 5 minutes apart with the subject supine and at rest for the 5 minutes.

3. Subjects taking concomitant medications of interest are excluded unless those medications are reviewed and discussed with the Medical Monitor or Study Physician and documented prior to enrolling the subject. If agreement is reached between the Investigator and Sponsor for the subject to continue in the study, all allowed medications should be maintained at a constant dose throughout the study.

4. The Principal Investigator deems any clinical laboratory test (screening test) abnormality clinically significant.

5. The subject has participated in other studies of investigational drugs or devices within 30 days prior to enrollment in this study (other than Study SPD426-405).

6. Current or relevant history of physical or psychiatric illness, any medical disorder that may require treatment or make the subject unlikely to fully comply with the requirements of the study or complete the study, or any condition that presents undue risk from the investigational product or study procedures.

7. The subject has a concurrent chronic or acute illness, disability, or other condition (including significant unexpected laboratory or electrocardiogram [ECG] findings) that might confound the results of the tests and/or measurements administered in this study, or that might have increased the risk to the subject.

8. Known or suspected intolerance or hypersensitivity to the investigational product(s), closely-related compounds, or any of the stated ingredients.

9. Prior enrollment failure or randomization in this study.

10. History of alcohol abuse or other substance abuse within the last year.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint in this study is the time (seconds) to onset of syncopal symptoms/near syncope as recorded in the tilt table tests performed at 1-hour post-dose on Days 2 and 3.

E.5.1.1

Timepoint(s) of evaluation of this end point

Day 2 and Day 3

E.5.2

Secondary end point(s)

Safety will be assessed by adverse events (AEs), clinical laboratory parameters, vital signs (systolic and diastolic BP, pulse, body temperature, and respiratory rate), and electrocardiograms (ECGs).

E.5.2.1

Timepoint(s) of evaluation of this end point

From screening to the follow-up phone call.

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)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

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

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

Czech Republic

Poland

Slovakia

United States

E.8.7

Trial has a data monitoring committee

Yes

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

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:

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

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)

There will be a follow-up telephone call 5 to 7 days after discharge or early termination, during which information on any new concomitant medications, (SAEs) or related AEs will be collected and any ongoing serious or non serious AEs will be followed up.
In some cases it may be necessary for subjects to return to the clinic for additional care and/or follow-up. All additional safety follow-up visits/follow-up telephone calls will be at the discretion of the Investigator and the Sponsor.

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

2013-05-06

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-05-02

P. End of Trial
P.	End of Trial Status	Completed

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