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Trial registered on ANZCTR


Registration number
ACTRN12610000379011
Ethics application status
Approved
Date submitted
7/05/2010
Date registered
11/05/2010
Date last updated
16/11/2010
Type of registration
Prospectively registered

Titles & IDs
Public title
Single-ascending dose of CEP 37251 in Healthy Postmenopausal Women
Scientific title
A Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Characterize the Safety, Pharmacokinetics, and Pharmacodynamics of CEP 37251 in Healthy Postmenopausal Women
Secondary ID [1] 251690 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Osteoporosis in Healthy Postmenopausal Women 257301 0
Condition category
Condition code
Reproductive Health and Childbirth 257449 257449 0 0
Menstruation and menopause

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
5 subcutaneous injection doses (sequentially) of CEP-37251 (0.03, 0.1, 0.3, 1.0, and 3.0 mg/kg) will be studied. After all 5 subcutaneous injection doses have been studied, an intravenous infusion dose of 0.3 mg/kg will be studied. At each dose level, subjects will be divided into 3 cohorts. The first cohort will consist of 2 subjects (1 subject receiving CEP-37251 and 1 subject receiving placebo), the second cohort will consist of 3 subjects (2 subjects receiving CEP-37251 and 1 subject receiving placebo), and cohort 3 will consist of 4 subjects (3 subjects receiving CEP-37251 and 1 subject receiving placebo). There will be a minimum of 30 minutes between the start of study drug administration for each subject within a cohort. Each subject in both the subcutaneous injection and intravenous infusion groups will receive one dose only. There will be a minimum of 1 week between dose administration of the 1st and subsequent cohort(s) for each dose level. There is no minumum wait time between administration of the 2nd and 3rd cohorts in each dose level. The 2nd and 3rd cohorts of a dose level can be dosed in non-sequential order and can be dosed on the same day.
Intervention code [1] 256432 0
Treatment: Drugs
Comparator / control treatment
Buffer solution containing 36 mM citric acid, 98 mM sodium phosphate, and 150 mM sodium chloride, pH 5.5 (identical in color and appearance to CEP-37251 drug product) will be used as placebo. The placebo will be provided as a 1 mL extractable volume in a 2 mL vial.
The placebo for the first 5 doses will be given as subcutaneous injection. The placebo for the 6 dose group will be given as intravenous infusion.
Control group
Placebo

Outcomes
Primary outcome [1] 258373 0
The primary objective of this study is to assess the safety of CEP 37251 given by subcutaneous injection or intravenous infusion to healthy postmenopausal women
Timepoint [1] 258373 0
Subjects will be continuously monitored for the occurrence of adverse events, clinical laboratory test results, immunoglobulin measurements, biochemical panel test results, vital signs measurements, 12 lead Electrocardiogram findings, physical examination findings, injection-site evaluation findings, concomitant medication usage, immunophenotyping test results, and immunogenicity test results (from baseline to end of study). Subjects will be monitored (remain) at the study site for 48hrs after dose administration.
Secondary outcome [1] 264106 0
To evaluate the following characteristic of CEP-37251 over 70 days following a single subcutaneous injection or an intravenous infusion to healthy postmenopausal women
-The pharmacokinetic profile of CEP-37251
Timepoint [1] 264106 0
Urine samples will be obtained before study drug administration (minus 24 and 0 hours), 12, 24, and 48 hours after the start of study drug administration and on days 4, 5, 7, 14, 21, 28, 56, and 70. Blood samples will be obtained before study drug administration (minus 24 and 0 hours), 24 and 48 hours after the start of study drug administration and on days 4, 5, 7, 14, 21, 28, 56, and 70.
Secondary outcome [2] 264148 0
To evaluate the following characteristic of CEP-37251 over 70 days following a single subcutaneous injection or an intravenous infusion to healthy postmenopausal women
- The pharmacodynamic effect of CEP-37251 as measured by markers of bone metabolism
Timepoint [2] 264148 0
Urine samples will be obtained before study drug administration (minus 24 and 0 hours), 12, 24, and 48 hours after the start of study drug administration and on days 4, 5, 7, 14, 21, 28, 56, and 70. Blood samples will be obtained before study drug administration (minus 24 and 0 hours), 24 and 48 hours after the start of study drug administration and on days 4, 5, 7, 14, 21, 28, 56, and 70.

Eligibility
Key inclusion criteria
1. The subject is a postmenopausal woman aged 40 years or greater but less than 75 years.
2.The subject is considered to be postmenopausal if at least 1 of the following criteria is met: 1a) aged 50 or more years and has had a lack of menses for 12 or more months 1b) aged 40 or more and less than 50 years, has had a lack of menses for 12 or more months, and serum estradiol is 20 ng/mL or less or follicular stimulating hormone (FSH) is 50 IU/L or greater 1c) aged 40 or more years and has had bilateral surgical oophorectomy 1d) aged 40 or more years, has had a hysterectomy, and serum estradiol is 20 ng/mL or less or FSH is 50 IU/L or greater
3. The subject has a body weight greater than 50 kg but no more than 100 kg with a body mass index (BMI) of 18 to 35 kg/m2
Minimum age
40 Years
Maximum age
75 Years
Sex
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1 The subject has received any of the following medications within the 6 months prior to enrollment: 1a) hormone replacement therapy 1b) selective estrogen receptor modulator (SERM) therapy such as raloxifene 1c) elemental calcium supplementation >1.5 g/day 1d) Vitamin D supplementation >1000 IU per day 1e) calcitriol or other Vitamin D analogs of calcitrol (eg, alfacalcidol, doxercalciferol, or paricalcitol) 1f) calcitonin or parathyroid hormone 1g) glucocorticoids and/or anabolic steroids
2 The subject has received bisphosphonates or fluoride within the 12 months prior to enrollment.
3 The subject has any of the following concomitant conditions: 3a) hypo- or hyperthyroidism. NOTE: Subjects with treated hypothyroidism with normal thyroid parameters may be allowed to participate in the study at the discretion of the investigator and medical monitor. 3b) hypo- or hyperparathyroidism 3c) recent fracture (within 6 months) 3d) osteomalacia, Paget’s Disease, osteopetrosis, osteogenesis imperfecta, or other bone disease 3e) rheumatoid arthritis or psoriatic arthritis 3f) acute osteoarthritis or gout 3g) chronic kidney disease or renal failure defined as an estimated glomerular filtration rate (eGFR) (by Modification of Diet in Renal Disease (MDRD) equation) 30 mL/min/1.73m2 or less
4 The subject is receiving immunosuppressant drugs.
5 The subject has evidence of severe, progressive, or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, psychiatric, or cerebral disease, or malabsorption syndrome.
6 The subject has a known history or evidence of malignancy, lymphoproliferative, or neoplastic disease with the exception of being successfully treated for basal or squamous cell carcinoma of the skin or cervical intraepithelial neoplasia.
7 The subject has a known or suspected hypersensitivity or idiosyncratic reaction to any compound present in the study drug or placebo.
8 The subject has habitually consumed, within the past 2 years, more than 21 units of alcohol per week, or has a history of alcohol, narcotic, or any other substance abuse as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR, American Psychiatric Association 2000). NOTE: A unit of alcohol is equal to approximately 30 ml of spirits, 100 ml of wine, or 260 ml of full-strength beer.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
5 subcutaneous injection doses (sequentially) of CEP-37251 (0.03, 0.1, 0.3, 1.0, and 3.0 mg/kg) will be studied. After all 5 subcutaneous injection doses have been studied, an intravenous infusion dose of 0.3 mg/kg will be studied. At each dose level, subjects will be divided into 3 cohorts. The first cohort will consist of 2 subjects (1 subject receiving CEP-37251 and 1 subject receiving placebo), the second cohort will consist of 3 subjects (2 subjects receiving CEP-37251 and 1 subject receiving placebo), and cohort 3 will consist of 4 subjects (3 subjects receiving CEP-37251 and 1 subject receiving placebo). There will be a minimum of 30 minutes between the start of study drug administration for each subject within a cohort. Each subject in both the subcutaneous injection and intravenous infusion groups will receive one dose only. There will be a minimum of 1 week between dose administration of the 1st and subsequent cohort(s) for each dose level. There is no minumum wait time between administration of the 2nd and 3rd cohorts in each dose level. The 2nd and 3rd cohorts of a dose level can be dosed in non-sequential order and can be dosed on the same day.
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Date of first participant enrolment
Anticipated
1/06/2010
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
54
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 256922 0
Commercial sector/Industry
Name [1] 256922 0
Cephalon, Inc.
Country [1] 256922 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Cephalon, Inc.
Address
41 Moores Road
Frazer, Pennsylvania 19355
Country
United States of America
Secondary sponsor category [1] 256191 0
Commercial sector/Industry
Name [1] 256191 0
Cephalon Australia Pty Ltd
Address [1] 256191 0
Level 2
37 Epping Road
Macquarie Park NSW 2113
Country [1] 256191 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 258928 0
Bellberry Limited
Ethics committee address [1] 258928 0
229 Greenhill Road
Dulwich SA 5065
Ethics committee country [1] 258928 0
Australia
Date submitted for ethics approval [1] 258928 0
05/05/2010
Approval date [1] 258928 0
07/06/2010
Ethics approval number [1] 258928 0

Summary
Brief summary
The purpose of this study is to characterize the safety, pharmacokinetics, and pharmacodynamics of CEP 37251 following single ascending doses in healthy postmenopausal women. This study is intended to identify a dose of CEP-37251 having a sustained effect on biomarkers of bone resorption.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 31133 0
Address 31133 0
Country 31133 0
Phone 31133 0
Fax 31133 0
Email 31133 0
Contact person for public queries
Name 14380 0
Jane Kelly
Address 14380 0
CMAX, A division of
Institute of Drug Technology (IDT) Australia Ltd
Level 5 East Wing
Royal Adelaide Hospital
North Terrace, Adelaide, 5000
S.A
Country 14380 0
Australia
Phone 14380 0
+61 8 8222 3931
Fax 14380 0
Email 14380 0
[email protected]
Contact person for scientific queries
Name 5308 0
Denise M. D’Andrea (Sr. Director, Clinical Pharmacology and Experimental Medicine)
Address 5308 0
41 Moores Road
Frazer, Pennsylvania 19355
Country 5308 0
United States of America
Phone 5308 0
001-610-738-6897
Fax 5308 0
Email 5308 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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