Clinical Trials Register

Summary
EudraCT Number:	2010-020342-98
Sponsor's Protocol Code Number:	UGL-OR1001
National Competent Authority:	Lithuania - SMCA
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2011-01-12
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Lithuania - SMCA

A.2

EudraCT number

2010-020342-98

A.3

Full title of the trial

A Double-Blind, Randomized, Repeat Dose, Parallel Group Study of Recombinant Human Parathyroid Hormone (rhPTH(1-31)NH2) tablets, or Placebo tablets, Compared to Open Label Forsteo in Postmenopausal Women with Osteoporosis

A.4.1

Sponsor's protocol code number

UGL-OR1001

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	Unigene Laboratories, 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	Recombinant human PTH(1-31)NH2
D.3.2	Product code	PTH(1-31)NH2
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	PARATHYROID HORMONE
D.3.9.1	CAS number	9002-64-6
D.3.9.3	Other descriptive name	recombinant human PTH(1-31)NH2
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	5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Forsteo
D.2.1.1.2	Name of the Marketing Authorisation holder	Eli Lilly
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Forsteo
D.3.4	Pharmaceutical form	Injection*
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	TERIPARATIDE
D.3.9.1	CAS number	52232-67-4
D.3.9.3	Other descriptive name	(1-34)-Human parathormone
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Postmenopausal Osteoporosis

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	12.1
E.1.2	Level	PT
E.1.2	Classification code	10031285
E.1.2	Term	Osteoporosis postmenopausal

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 characterize percent change from baseline in bone mineral density (BMD) at L1-L4 axial lumbar spine after 24 weeks of once daily treatment of 5 mg tablets of rhPTH(1 31)NH2.

E.2.2

Secondary objectives of the trial

To evaluate the safety and tolerability after 24 wks of once daily (SID) treatment (treat.) of 5 mg tablets (tabs) of rhPTH(1-31)NH2;to characterize % change from baseline (BL) in BMD at L1-L4 axial lumbar spine after 24 wks of SID treat. of matching placebo tabs/of open label Forsteo SC injection;to demonstrate a statistically significant increase in BMD using DXA in L1-L4 lumbar spine after 24 wks of treat. with rhPTH(1-31)NH2 tabs compared to BL;to evaluate the change in BMD using DXA in the total hip,trochanter and femoral neck after 24 wks of treat. with rhPTH(1-31)NH2 tabs/ with open label Forsteo SC injection compared to BL; to characterize % change from BL in -CrossLaps and total PINP as markers for bone turnover after 4 wks, 12 wks, and 24 wks of SID treat. with 5 mg rhPTH(1-31)NH2 tabs; to characterize PK profile of 5 mg rhPTH(1-31)NH2 tabs after the first dose and at the end of treat.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

•Informed Consent: Provide written informed consent before initiation of any study related procedures.
•Ambulatory postmenopausal women in good health. Menopausal status: Patient should be at least 5 years postmenopausal which can be ≥5 years of spontaneous amenorrhea or ≥5 years postsurgical bilateral oophorectomy. Use follicle stimulation hormone (FSH) levels >40 mIU/mL to confirm surgical postmenopausal status where bilateral oophorectomy status is uncertain.
•Age ≥ 45 years, ≤80 years.
•BMD Values: Diagnosis of osteoporosis on the basis of an axial lumbar spine, femoral neck or total hip BMD which is below the mean for premenopausal women by a magnitude of at least 2.5 SD or 2.0 SD, if there is a documented (x-ray) history of a vertebral fragility fracture.
•Suitable Vertebrae: Two or more vertebrae in the range of L1 to L4 that are suitable for BMD measurement by DXA.
•No clinically significant abnormal findings in the medical history or physical examination.
- Negative screen for Hepatitis B and C, HIV and drugs of abuse at screening.
•Laboratory Values:
- Total serum Ca, albumin-adjusted Ca, P, and Mg++ within normal range.
- No clinically significant abnormal laboratory values at the screening assessment.

E.4

Principal exclusion criteria

•BMI ≥33 kg/m2
•Illnesses:
- Liver function: Known hepatic or biliary abnormalities including Gilbert's syndrome.
- Clinically significant abnormal liver function tests (ALT, AST, GGT, alkaline phosphatase, total bilirubin).
- Abnormal kidney function tests: Creatinine clearance ≤30 ml/min; urinary calcium/creatinine ratio greater than 1.1 mmol/mmol on second morning voided specimen; or serum creatinine concentration exceeding 2 mg per deciliter (177 μmol per liter
- Medical illness: Presence of acute or chronic illness or history of chronic illness which, in the judgment of the Investigator, makes participation in the study medically inappropriate.
- History of pancreatitis, osteosarcoma, gout, or kidney stones (calcium oxalate or calcium phosphate).
- Uncontrolled hypertension, significant gastrointestinal abnormalities, uncontrolled diabetes mellitus, any psychotic mental illness, uncorrected endocrine dysfunction, or significantly impaired respiratory or renal function.
- Medical conditions which might alter bone metabolism, including: hyperparathyroidism, hypoparathyroidism, untreated hyperthyroidism, untreated hypothyroidism, Paget's disease, myeloma, malabsorption, Cushing's syndrome, hypocalcemia, hypercalcemia, hypophosphatemia, hyperphosphatemia, hypomagnesemia, hypermagnesemia, osteopetrosis, osteomalacia, rheumatoid arthritis and recent (within one year) history of non-traumatic fracture or prolonged bed rest.
- History of musculoskeletal disease. However, patients with conditions such as fibromyalgia, osteoarthritis, and degenerative disc disease may be enrolled at the discretion of the Investigator and Medical Monitor.
- History of cancer within 5 years of enrollment other than basal cell carcinoma and carcinoma in situ.
•History of clinically significant Cardiovascular Disease and/or Postural Hypotension:
- QT/QTc prolongation: A marked baseline prolongation of QT/QTc interval (e.g., QTc interval > 450 msec on the screening ECG).
- Torsades des Pointes: A history of risk factors for Torsades de Pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome).
•Electrocardiogram: Any clinically relevant abnormality identified on the 12-lead surface electrocardiogram (ECG).
•History of Surgery within 60 days of enrollment.
•Evidence of Alcohol or Substance Abuse that the Investigator believes would interfere with understanding or completing the study.
•Laboratory Findings:
- Albumin-adjusted serum calcium greater or less than 10% of the normal reference range of the analytical laboratory.
- Urine calcium greater than the normal reference range of the laboratory.
- PTH(1-84) greater than the normal reference range of the analytical laboratory.
- Abnormal Alkaline Phosphatase.
- Vitamin D: Vitamin D insufficiency defined as a 25 hydroxyvitamin D level <15 ng/mL.
•DXA:
- Any condition or disease that may interfere with the ability to have a DXA scan or to evaluate a DXA scan, for example, spinal fusion, pedicle screws, history of vertebroplasty, or degenerative disease that results in insufficient number of evaluable lumbar vertebrae, or more than 1 lumbar vertebral fracture in L1 through L4.
- Bilateral hip replacements.
•Contraindicated Medications: Contraindicated medications are defined in Table 4 2.
•Osteosarcoma Risk: Patients at increased risk of osteosarcoma such as those with Paget’s disease of bone or any prior external beam or implant radiation therapy involving the skeleton.
•Contraindications: Contraindications to therapy with teriparatide, calcium or Vitamin D.
•Interfering Medications: Vitamin A in excess of 10,000 IU per day, heparin, lithium, or anticonvulsant medications including primidone, phenobarbital, phenytoin, and carbamazepine.
•Investigational Drug Exposure: Administration of any investigation drug within 90 days preceding the first dose of study drug.

E.5 End points

E.5.1

Primary end point(s)

Percent change from baseline in the axial lumbar spine BMD values over a 24 week period.

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

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

Yes

E.8.1.7.1

Other trial design description

repeat dose

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

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

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

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

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 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

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	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)	Yes
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	No
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	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	35
F.4.2	For a multinational trial
F.4.2.1	In the EEA	93
F.4.2.2	In the whole clinical trial	93

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

2011-04-01

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-03-18

P. End of Trial
P.	End of Trial Status	Prematurely Ended

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials