Clinical Trials Register

Summary
EudraCT Number:	2009-018029-57
Sponsor's Protocol Code Number:	LT-NS001-003
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2010-03-18
Trial 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

2009-018029-57

A.3

Full title of the trial

A Double-Blind, Double-Dummy, Randomized, Active-Comparator, Arthritis Non-Inferiority Study of LT-NS001 versus Naprosyn® for Twelve Weeks in Osteoarthritis Patients to Compare Endoscopic Gastric Ulcer Rates

A.3.2

Name or abbreviated title of the trial where available

Nature Trial

A.4.1

Sponsor's protocol code number

LT-NS001-003

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	Logical Therapeutics Inc.
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
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	LT-NS001
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.3.9.2	Current sponsor code	LT-NS001
D.3.9.3	Other descriptive name	(Naproxen pro-drug)
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	600 mg
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	LT-NS001
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	600 mg
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	Comparator
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	Naprosyn® 500mg tablets
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche
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	Naprosyn®
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.3.8	INN - Proposed INN	NAPROXEN
D.3.9.1	CAS number	22204-53-1
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	500
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 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

osteoarthritis of the knee

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

Primary (GI Safety): To compare the cumulative incidence of patients with gastric ulcer by endoscopy (EGD) for Arm A vs Arm B
Secondary (for Arm A vs Arm B):
1. To demonstrate non-inferior pain control in an index osteoarthritic knee joint
2. To compare overall gastric injury rates by EGD
3. To compare tolerability and retention on study drug

E.2.2

Secondary objectives of the trial

Exploratory (for Arm A vs B):
1. To compare changes in stiffness, function and total response in an index osteoarthritic knee joint
2. To evaluate GI and overall safety of LT-NS001 1200 mg versus Naprosyn® 500 mg b.i.d. for 12 weeks
3. To develop population PK data for analysis of covariates

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Written Informed consent.
• Age 45–80 years, inclusive.
• Osteoarthritis of knee.
• Appropriate candidate for chronic NSAID therapy due to moderate or severe pain on most days in the previous 28 days prior to screening.
• Baseline (pre-dose) index joint WOMAC pain index ≥40 mm, after a 14 day NSAID washout and with no analgesia on the entire day prior to, and on the day of the WOMAC questionnaire (until completed).
• Body mass index ≤42 kg/m2.
• Patients of reproductive potential (males and females) agree to use two acceptable methods of birth control during the study. Abstinence is acceptable for patients who sign an additional statement of risk.

E.4

Principal exclusion criteria

Medical History / Examination:
• Pregnant or nursing women.
• History of documented gastrointestinal bleeding, obstruction or perforation.
• History of a documented symptomatic gastroduodenal ulcer (not including an asymptomatic ulcer detected by endoscopic screening) in the previous 5 years.
• Baseline upper gastroduodenal endoscopy with ulcer or >2 total erosions.
• Inflammatory bowel disease, celiac disease/gluten enteropathy, Whipple’s disease, or other malabsorptive disease.
• Resting supine blood pressure >180 mm Hg systolic or >105 mm Hg diastolic, with no change in anti-hypertensive medication for 28 days prior to Screening if the patient is receiving anti-hypertensive medication.
• New York Heart Association Class III or IV cardiac function.
• Recent (6 months) stroke or myocardial infarction.
• History of cancer except for excised basal cell or squamous cell carcinoma of the skin >3 years ago.
• Active or recurrent infection.
• Psychiatric or neurologic disease precluding participation based on inadequate consent or inability to follow study instructions.
• Any other medical condition that would prohibit study participation in the view of the Principal Investigator.
• Lack of peripheral venous access.
• Active alcohol abuse / drug addiction (including cannabis products) in the previous 2 years.
Medications:
• Allergy to naproxen, acetylsalicylic acid or other NSAID drug.
• Severe naproxen intolerance in the past.
• No intra-articular injections in the 28 days prior to screening.
• Use of a second NSAID including aspirin within 14 days prior to baseline endoscopy, or planned use during study participation.
• Use of an anti-coagulant or anti-platelet drug within 14 days prior to baseline endoscopy or planned use during study participation.
• Use of proton-pump inhibitors (PPI), type 2 histamine blockers (H2 blocker), antacids, binding agents including bile acid sequestrants, pancreatic replacement, cholinesterase inhibitors or specified analgesics including narcotics within 14 days prior to baseline endoscopy or planned use during study participation.
• Treatment with an investigational agent (including device) within 28 days or 5 investigational drug half-lives (whichever is longer) of Screening, current participation in another research study, or participation in more than 3 research studies in the previous 12 months.
Screening Laboratory Tests:
• Positive H. pylori stool antigen test
• Hgb <11.5 gm/dL (women) or <12.5 gm/dL (men).
• Calculated GFR (MDRD) <30 mL/min/1.73 m2.
• AST or ALT >1.5 times upper limit of normal.
• Positive hepatitis B surface antigen (HBsAg).
• Positive anti-hepatitis C (HCV) IgG antibody.
• Positive anti-human immunodeficiency virus (HIV) 1/2 IgG antibody.

E.5 End points

E.5.1

Primary end point(s)

Primary (GI Safety): Cumulative incidence of patients with gastric ulcer by endoscopy at week 12 for Arm A versus Arm B

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

Yes

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)

Yes

E.8.2.2

Placebo

Yes

E.8.2.3

Other

Information not present in EudraCT

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

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

F. Population of Trial Subjects
F.1 Age Range
F.1.1	Trial has subjects under 18	No
F.1.1.1	In Utero	Information not present in EudraCT
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	Information not present in EudraCT
F.1.1.3	Newborns (0-27 days)	Information not present in EudraCT
F.1.1.4	Infants and toddlers (28 days-23 months)	Information not present in EudraCT
F.1.1.5	Children (2-11years)	Information not present in EudraCT
F.1.1.6	Adolescents (12-17 years)	Information not present in EudraCT
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	Yes
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2010-03-18.	Yes
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
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	30
F.4.2	For a multinational trial
F.4.2.1	In the EEA	30
F.4.2.2	In the whole clinical trial	534

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

2010-04-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2010-04-26

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2010-12-08

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