Open-Label Study to Evaluate the Inter-subject Variability of Single Dose Prolia Pharmacokinetics and Pharmacodynamics, Administered by Subcutaneous Injection in Healthy Postmenopausal Women

• Register: ANZCTR
• Last refreshed on: 14 June 2021
• Main ID: ACTRN12621000728831
• Date of registration: 10/06/2021
• Prospective Registration: Yes
• Primary sponsor: Christchurch Clinical Studies Trust
• 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
• Date of first enrolment: 14/07/2021
• Target sample size: 20
• Recruitment status: Not yet recruiting
• URL: https://anzctr.org.au/ACTRN12621000728831.aspx
• Study type: Interventional
• Study design: Purpose: Treatment; Allocation: Non-randomised trial; Masking: Open (masking not used);Assignment: Single group;Type of endpoint: Pharmacokinetics;
• Phase: Phase 4

Countries of recruitment

New Zealand

Contacts

• Name: Dr Chris Wynne

• Name: Dr Chris Wynne

Key inclusion & exclusion criteria

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

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


Age minimum: 40 Years
Age maximum: No limit
Gender: Females

Health Condition(s) or Problem(s) studied

Musculoskeletal - Osteoporosis

Osteoporosis;
Osteoporosis

Reproductive Health and Childbirth - Menstruation and menopause

Intervention(s)

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.

Primary Outcome(s)

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.
[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(s)

To assess the safety and tolerability of a single 6 mg SC dose of EU-Prolia, administered in healthy postmenopausal women.[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.

]

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,
[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 ID(s)

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

Source(s) of Monetary Support

Christchurch Clinical Studies Trust

Ethics review

Status: Approved
Approval date: 19/04/2021
Contact:

Southern Health and Disability Ethics Committee