Clinical Trials Register

Summary
EudraCT Number:	2006-005807-32
Sponsor's Protocol Code Number:	OTA105256
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:	2007-05-15
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

2006-005807-32

A.3

Full title of the trial

A randomized, double-blind, placebo-controlled, dose ranging study to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of GSK221149A administered intravenously and the pharmacokinetics of GSK221149A administered orally to healthy, pregnant females with uncomplicated pre-term labor between 30 0/7 - 35 6/7 weeks gestation

A.4.1

Sponsor's protocol code number

OTA105256

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	GlaxoSmithKline Research and Development
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	GSK221149A
D.3.2	Product code	GSK221149A
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	820957-38-8
D.3.9.2	Current sponsor code	GSK221149A
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	125
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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	GSK221149A
D.3.2	Product code	GSK221149A
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	820957-38-8
D.3.9.2	Current sponsor code	GSK221149A
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.8
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Uncomplicated preterm labour

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	8.1
E.1.2	Level	LLT
E.1.2	Classification code	10023555
E.1.2	Term	Labour premature

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Parts A and B
1. To describe the maternal safety and tolerability of GSK221149A administered
intravenously to healthy pregnant women in PTL between 340/7 and 356/7 weeks
gestation
2. To describe the fetal safety and tolerability of GSK221149A administered
intravenously to healthy pregnant women in PTL between 340/7 and 356/7 weeks
gestation
3. To evaluate the pharmacodynamics of GSK221149A in pregnant women in pre-term labor between 340/7 and 356/7 weeks gestation
4. To characterize the pharmacokinetics of GSK221149A administered intravenously to pregnant females in pre-term labor between 340/7 and 356/7 weeks gestation

Part C
Same objectives as above but administered intravenously to pregnant females in pre-term labor between 30 0/7 and 35 6/7 weeks gestation

E.2.2

Secondary objectives of the trial

Parts A and B
1. To describe the effect of maternal treatment with GSK221149A on short term
neonatal growth and development
2. To characterize the pharmacokinetics of GSK221149A administered orally to
pregnant females in pre-term labor between 34 0/7 and 35 6/7 weeks gestation as data permit
Part C
1. To describe the effect of maternal treatment with GSK221149A on short term
neonatal growth and well-being

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Part A and Part B
1. At least 18 years of age
2. 340/7 -356/7 weeks (best obstetric estimate, preferably first trimester ultrasound) with singleton pregnancy
3. Symptoms of pre-term labor: ≥6 uterine contractions per hour, each of at least 30 sec in duration as measured by tocodynamometry, with cervical dilatation ≤3cm
4. Intact fetal membranes

Part C
1. At least 18 years of age
2. 300/7 -356/7 weeks (best obstetric estimate, preferably first trimester ultrasound) with singleton pregnancy
3. Symptoms of pre-term labor: contractions at a frequency of 4 per 30 min or 6 per
hour, each of at least 30 sec in duration and confirmed by tocodynamometry
4. Cervical dilatation ≥2 cm or a definitive cervical change from baseline assessment.
Subjects can not exceed a maximum cervical dilation of 4 cm to be included in this
study at the time of screening.
5. Intact fetal membranes

E.4

Principal exclusion criteria

1. Any clinically relevant abnormality identified on the screening examination or any
other medical condition or circumstance making the patient (mother and/or fetus)
unsuitable for participation in the study
2. Any clinically relevant pre-existing or pregnancy-related co-morbid condition that
may affect maternal pregnancy outcome or neonatal outcome (eg. hypertension,
diabetes mellitus, bleeding/clotting diathesis)
3. Known fetal intrauterine growth restriction or fetal congenital anomaly
4. Abnormal modified biophysical profile (NST is non-reactive and AFI <5)
5. Participation in another interventional (i.e any study involving an investigational
product or device) clinical trial during the current pregnancy
6. Abuse of alcohol, defined as an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units. One unit is equivalent to a half-pint
(220mL) of beer or 1 (25mL) measure of spirits, or 1 glass (125mL of wine)
7. History of anaphylaxis or anaphylactoid reactions, or severe allergic responses to
drugs
8. Known to be positive for hepatitis C antibody, hepatitis B surface antigen or HIV on prenatal laboratory results
9. Use of prescription drugs that are potent CYP3A4 inhibitors, within 7 days or 5 halflives (whichever is longer) prior to first dose of medication. Tocolytics are prohibited within 6 hours of enrolment (see exclusion #15)
10. Use of dietary/herbal supplements including (but not limited to) St. John's wort,
kava, ephedra (ma huang), gingko biloba, DHEA, yohimbe, saw palmetto, ginseng,
and red yeast rice (2-fold greater than the recommended daily allowance of 1200 mg
per day) within 7 days prior to first dose of medication
11. Consumption of grapefruit or grapefruit juice within 3 days prior to first dose of
medication
12. QTc > 450 msec (either QTcb or QTcf, machine or manual overread, on single or
average QTc value of triplicate ECGs obtained over a brief recording period.)
13. QTc > 480 msec for patients with Bundle Branch Block
14. Use of illicit drugs or positive urine drug screen during pregnancy
15. Any tocolytic therapy within 24 hours
16. Any contraindication to tocolytic therapy, including (but not limited to) suspected
intrauterine infection, vaginal bleeding, pre-eclampsia/eclampsia
17. Trauma within 48 hours of presentation in preterm labor
18. Subjects treated with dexamethasone

E.5 End points

E.5.1

Primary end point(s)

Parts A and B:
1. Maternal safety and tolerability, (vital signs, ECGs, clinical laboratory tests, adverse events) during acute therapy and for approximately 24 hours after the initiation of therapy compared to placebo and baseline
2. Assessment of fetal heart rate before, during and after therapy and amniotic fluid
index (AFI) measurements before, during and after therapy with GSK221149A
compared to placebo and baseline
3. Elucidation of the concentrations vs. effect relationship for GSK221149A, using
number of contractions/hour as the pharmacodynamic end-point

Part C
1. Maternal safety and tolerability, (vital signs, ECGs, clinical laboratory tests, adverse events) during acute therapy and for approximately 48 hours after the initiation of therapy compared to placebo and baseline
2. Assessment of fetal heart rate and amniotic fluid index (AFI) measurements before, during, and after treatment with GSK221149A compared to placebo and baseline
3. Proportion of patients who achieve >= 50% reduction in number of contractions [>
30 secs] per hour from baseline together with no cervical dilation increase within the
first 6 hours of therapy

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

Yes

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.8.3

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

Information not present in EudraCT

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

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

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

F. Population of Trial Subjects
F.1 Age Range
F.1.1	Trial has subjects under 18	No
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	No
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	No
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	No
F.3.3.3	Pregnant women	Yes
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	10
F.4.2	For a multinational trial
F.4.2.1	In the EEA	45
F.4.2.2	In the whole clinical trial	90

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

2007-06-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2007-06-29

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2008-11-17

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