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Trial registered on ANZCTR


Registration number
ACTRN12621000728831
Ethics application status
Approved
Date submitted
19/03/2021
Date registered
10/06/2021
Date last updated
10/06/2021
Date data sharing statement initially provided
10/06/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Open-Label Study to Evaluate the Inter-subject Variability of Single Dose Prolia Pharmacokinetics and Pharmacodynamics, Administered by Subcutaneous Injection in Healthy Postmenopausal Women
Scientific title
Open-Label Study to Evaluate the Inter-subject Variability of Single Dose Prolia Pharmacokinetics and Pharmacodynamics, Administered by Subcutaneous Injection in Healthy Postmenopausal Women
Secondary ID [1] 304450 0
To provide PD data of a single 6 mg SC dose of EU-Prolia, administered in healthy postmenopausal women assessed by Procollagen type 1 N-terminal propeptide (P1NP), bone specific alkaline phosphatase (BSAP) and osteocalcin (OC).
Accessed by Procollagen type 1 N-terminal propeptide (P1NP), bone specific alkaline phosphatase (BSAP) and osteocalcin (OC) assessed by plasma assay
Universal Trial Number (UTN)
U1111-1265-3364
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Osteoporosis 321188 0
Condition category
Condition code
Musculoskeletal 318981 318981 0 0
Osteoporosis
Reproductive Health and Childbirth 319860 319860 0 0
Menstruation and menopause

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Approximately 20 healthy post menopausal women will each receive a single 6mg dose of Prolia, as an injection under the skin in the abdomen. The SC injection will be given by a registered nurse.
Intervention code [1] 320051 0
Treatment: Drugs
Comparator / control treatment
No contol group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 326901 0
The following PK parameters will be determined for prolia,
Cmax-Maximum concentration of the investigational product, obtained directly from the observed concentration versus time data.
AUC0-t Area under the serum concentration time curve of the IP, up to time t, where t is the last time point with concentrations above the LLOQ.
AUC0-inf Comprised of AUC0-t and AUC extrapolated from time t to time infinity, where t is the last time point with a concentration above the lower limit of quantitation (LLOQ); calculated as AUC0-t + Ct/kel
tmax -Time to attain maximal concentration.
Kel-Elimination rate constant.
t½-Terminal elimination half-life.
Vz/F -Volume of distribution.
CL/F -Apparent clearance.
Timepoint [1] 326901 0
Pre-dose 12 hours, post-dose 24 hours post-dose, 48 hours post-dose, 72 hours post-dose, 96 hours post-dose, 120 hours post-dose, 144 hours post-dose, 192 hours post-dose, 216 hours post-dose, 264 hours post-dose, 336 hours post-dose, 504 hours post-dose, 672 hours post-dose, 1008 hours post-dose, 1344 hours post-dose, 1680 hours post-dose, 2016 hours post-dose, 2256 hours post-dose, 2684 hours post-dose
Secondary outcome [1] 393044 0
To provide PD data of a single 6 mg SC dose of EU-Prolia, administered in healthy postmenopausal women assessed by Procollagen type 1 N-terminal propeptide (P1NP), bone specific alkaline phosphatase (BSAP) and osteocalcin (OC).
Assessed by Procollagen type 1 N-terminal propeptide (P1NP), bone specific alkaline phosphatase (BSAP) and osteocalcin (OC) assessed by plasma assay,
Timepoint [1] 393044 0
Pre-dose 12 hours, post-dose 24 hours, post-dose 48 hours, post-dose 72 hours, post-dose 96, hours post-dose 120 hours, post-dose 144 hours, post-dose 192 hours, post-dose 216 hours, post-dose 264 hours, post-dose 336 hours, post-dose 504 hours, post-dose 672 hours, post-dose 1008 hours, post-dose 1344 hours, post-dose 1680 hours. post-dose 2016 hours, post-dose 2256 hours, post-dose 2684 hours
Secondary outcome [2] 393045 0
To assess the safety and tolerability of a single 6 mg SC dose of EU-Prolia, administered in healthy postmenopausal women.
Timepoint [2] 393045 0
Adverse events will be assessed at each study visit on Days 1, 2, 3, 4, 5, 6, 7, 8, 9 ,10,12, 15,22,29, 43,57, 71, 85, 99, 112 This assessment will be a combination of physical examination, vital signs, ECGs and safety laboratory results of Haematology, Biochemistry, urinalysis
Very common side effects (reported in at least 10 in 100 people receiving Prolia include, Extremity (hand or foot) pain, Musculoskeletal (muscle / bone) pain. Common side effects (reported in at least 1 in 100 people, but less than 10 in 100) include: Upper breathing tract infections (including throat and sinus infections), Urine / bladder infection, Sciatica (nerve pain from the lower back), Constipation / abdominal discomfort, Rash / eczema / hair loss. Uncommon side effects (reported in at least 1 in 1000 people, but less than 1 in 100) include: Diverticulitis (inflamed pouches in the lining of the intestine), Skin infection / ear infection, Skin reaction against the drug.
Rare side effects (reported in less than 1 in 1000 people) include: Serious allergic / hypersensitivity reactions, Low calcium levels, which can be serious, •steonecrosis (serious, painful, premanent bone breakdown) of the jaw. Unusual fractures (breaks) of the thigh bone.

Eligibility
Key inclusion criteria
Evidence of clinically relevant pathology, especially prior diagnosis of bone disease, active malignancy, renal disease
Previous treatment with denosumab.
Receipt of any therapy that may significantly affect bone turnover, e.g., bisphosphonates within 12 months; or estrogens, selective estrogen receptor modulators, calcitonin, parathyroid hormone, high doses of Vitamin D (Greater than 1,000 IU daily), anabolic steroids, systemic glucocorticosteroids, or calcitriol within 6 months prior to IP administration.
Osteonecrosis of the jaw (ONJ) or risk factors for ONJ such as invasive dental procedures (e.g., tooth extraction, dental implants, oral surgery within 6 months prior to IP administration), poor oral hygiene, periodontal, and/or pre-existing dental disease.
.Evidence of hypocalcaemia, Known vitamin D deficiency.
Any current active infection, Positive test for Hepatitis B surface antigen (HBsAg), Hepatitis C virus (HCV) antibody or Human Immunodeficiency Virus (HIV) at screening.
A recent history of major surgery (within 3 months prior to IP administration).
History or presence of malignancy
Minimum age
40 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Evidence of clinically relevant pathology, especially prior diagnosis of bone disease, active malignancy, renal disease
Previous treatment with denosumab.
Receipt of any therapy that may signi?cantly affect bone turnover, e.g., bisphosphonates within 12 months; or estrogens, selective estrogen receptor modulators, calcitonin, parathyroid hormone, high doses of Vitamin D (Greater than 1,000 IU daily), anabolic steroids, systemic glucocorticosteroids, or calcitriol within 6 months prior to IP administration.
Osteonecrosis of the jaw (ONJ) or risk factors for ONJ such as invasive dental procedures (e.g., tooth extraction, dental implants, oral surgery within 6 months prior to IP administration), poor oral hygiene, periodontal, and/or pre-existing dental disease.
.Evidence of hypocalcemia, Known vitamin D deficiency.
Any current active infection, Positive test for Hepatitis B surface antigen (HBsAg), Hepatitis C virus (HCV) antibody or Human Immunodeficiency Virus (HIV) at screening.
A recent history of major surgery (within 3 months prior to IP administration).
History or presence of malignancy

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 4
Type of endpoint/s
Pharmacokinetics
Statistical methods / analysis
In general, data will be summarized using descriptive statistics (e.g., arithmetic mean, median, standard deviation, coefficient of variation, minimum, maximum; and geometric mean and geometric coefficient of variation as needed) or frequency counts and percentages, as appropriate to the type of data. Baseline will be defined as the last available, valid, non-missing assessment (scheduled or unscheduled) prior to dosing.
Only data from protocol scheduled visits/time points will be included in the summary tables. Data from unscheduled visits/time points will not be included in the summary tables but will be included in the figures and listings if indicated.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
14/07/2021
Actual
Date of last participant enrolment
Anticipated
31/08/2021
Actual
Date of last data collection
Anticipated
30/10/2021
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment outside Australia
Country [1] 23548 0
New Zealand
State/province [1] 23548 0
Canterbury

Funding & Sponsors
Funding source category [1] 308148 0
Commercial sector/Industry
Name [1] 308148 0
Christchurch Clinical Studies Trust
Country [1] 308148 0
New Zealand
Primary sponsor type
Commercial sector/Industry
Name
Christchurch Clinical Studies Trust
Address
264 Antigua Street Christchurch 8011
Country
New Zealand
Secondary sponsor category [1] 308912 0
None
Name [1] 308912 0
Address [1] 308912 0
Country [1] 308912 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308133 0
Southern Health and Disability Ethics Committee
Ethics committee address [1] 308133 0
Ministry of Health 133 Molesworth Street PO Box 5013 Wellington 6011
Ethics committee country [1] 308133 0
New Zealand
Date submitted for ethics approval [1] 308133 0
11/03/2021
Approval date [1] 308133 0
19/04/2021
Ethics approval number [1] 308133 0
21/STH/72

Summary
Brief summary
Single-center, single-arm, open-label study of Prolia administered subcutaneously in healthy post menopausal women.
The study is designed to provide single-dose pharmacokinetic inter-subject variability data for prolia, to optimize study design (including sample size calculation) for a proposed Prolia biosimilar pivotal PK study.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 109654 0
Dr Chris Wynne
Address 109654 0
Christchurch Clinical studies Trust 264 Antigua Street Christchurch 8011
Country 109654 0
New Zealand
Phone 109654 0
+64337294764
Fax 109654 0
Email 109654 0
[email protected]
Contact person for public queries
Name 109655 0
Chris Wynne
Address 109655 0
Christchurch Clinical studies Trust 264 Antigua Street Christchurch 8011
Country 109655 0
New Zealand
Phone 109655 0
+64337294764
Fax 109655 0
Email 109655 0
[email protected]
Contact person for scientific queries
Name 109656 0
Chris Wynne
Address 109656 0
Christchurch Clinical studies Trust 264 Antigua Street Christchurch 8011
Country 109656 0
New Zealand
Phone 109656 0
+64337294764
Fax 109656 0
Email 109656 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
11077Informed consent form  [email protected]
11078Study protocol  [email protected]



Results publications and other study-related documents

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No documents have been uploaded by study researchers.

Documents added automatically
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