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Trial registered on ANZCTR


Registration number
ACTRN12618000013268
Ethics application status
Approved
Date submitted
29/11/2017
Date registered
10/01/2018
Date last updated
17/07/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Comparison of pharmacokinetics, safety, tolerability, and pharmacodynamics (PK/PD) of Stelis Teriparatide [rh-PTH (1-34)] with Forsteo® and Forteo® in healthy volunteers
Scientific title
A single center, randomized, double blind, 3-treatment, 3-period, single-dose, cross over, comparative Phase-1 study to evaluate pharmacokinetics, safety, tolerability, and pharmacodynamics (PK/PD) of Stelis Teriparatide [rh-PTH (1-34)] with Forsteo® and Forteo® (teriparatide, Eli Lilly) in healthy volunteers following subcutaneous single dose administration of 20 µg Teriparatide
Secondary ID [1] 293491 0
NIL
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
OSTEOPOROSIS 305676 0
Condition category
Condition code
Musculoskeletal 304897 304897 0 0
Osteoporosis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Test Product (T): Stelis Teriparatide [rh-PTH (1-34)]
The volunteers will be administered with a single dose of 20 mcg Teriparatide from Test product product through subcutaneous injection on either side of anterior abdominal wall, alternating between opposite sites in the 3 periods by trained study team member in accordance with the randomization schedule in this 3 way cross over design study.
The Stelis Teriparatide [rh-PTH (1-34)] injection is supplied in a cartridge as 250 micrograms of Teriparatide [rh-PTH (1-34)] per mL of solution. The injection is supplied as sterile, colorless, clear, isotonic solution intended for subcutaneous injection. The solution contains acetate buffer with mannitol as tonicity agent and metacresol as preservative.
The cartridge is supplied as with filled volume of 3.2 mL of solution along with reusable pen to be adequate for multiple usage. Pen can deliver 28 dosages of 20 micrograms each delivered in 80 microliters of solution. Pen is approved as a medical device with ‘CE mark’ by notified body based in United Kingdom authorized by Medicines and Healthcare Products Regulatory Agency (MHRA-UK).
The formulation components, intended dosage, and route of administration of the Test product is similar to the innovator reference product Forsteo® and Forteo®. The test formulation is supplied in an USP type-1 Glass cartridge, bromobutyl plunger. Each mL of solution contains 250 µg Stelis Teriparatide [rh-PTH (1-34)], 410 µg acetic acid – glacial, 100 µg sodium acetate, 45.4 mg mannitol, 3.0 mg meta-cresol and water for injections. In addition, hydrochloric acid solution 10% q.s. and/or sodium hydroxide solution 10% q.s. have been added to adjust product pH.

The comparability criteria for Stelis Teriparatide [rh-PTH(1-34)] biosimilar is established for the finished product via a quality target product profile (QTPP). The QTPP was based on data collected on the reference medicinal product Forsteo® and Forteo®, including publicly available information and data obtained from extensive characterization of the reference medicinal product. QTPP formed the basis for the development of the biosimilar product and its manufacturing process.
Each of the 3 treatment periods will be separated by a washout period of 7 days and the subjects will be followed for safety for +/- 7 days after the last dose of the Test/Reference product administered in the study.
Intervention code [1] 299730 0
Treatment: Drugs
Comparator / control treatment
Comparator/Reference Product - Teripratide formulations (Forsteo® and Forteo®) being marketed by Eli Lily in EU and USA will be used as the two reference products or active controls in the study. Forsteo® is the registered brand name in EU whereas Forteo® is the registered brand name in USA.
The volunteers will be administered with a single dose of 20 mcg Teriparatide from Comparator product or reference product through subcutaneous injection on either side of anterior abdominal wall, alternating between opposite sites in the 3 periods by trained study team member in accordance with the randomization schedule in this 3 way cross over design study.
Each of the 3 treatment periods will be separated by a washout period of 7 days and the subjects will be followed for safety for +/- 7 days after the last dose of the Test/Reference product administered in the study.
Control group
Active

Outcomes
Primary outcome [1] 304088 0
Area under the concentration-time curve (AUC) from the time of drug administration to the last quantifiable concentration (AUC0-t). Plasma concentrations of rh-PTH(1-34) will be measured using validated immunoassay with chemiluminescence detection technique.
Timepoint [1] 304088 0
Samples for estimation of PK profile of teriparatide will be drawn pre-dose (within 30 minutes prior to dosing), and post dose at 5, 10, 15, 20, 25, 30, 35, 40, 50 minutes and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, and 12 hours (Primary endpoint).
Primary outcome [2] 304089 0
Maximum observed concentration ( Cmax). Plasma concentrations of rh-PTH(1-34) will be measured using validated immunoassay with chemiluminescence detection technique .
Timepoint [2] 304089 0
Samples for estimation of PK profile of teriparatide will be drawn pre-dose (within 30 minutes prior to dosing), and post dose at 5, 10, 15, 20, 25, 30, 35, 40, 50 minutes and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, and 12 hours (Primary endpoint).
Primary outcome [3] 304090 0
Area under the concentration-time curve (AUC) from the time of drug administration to infinity (AUC0-inf). Plasma concentrations of rh-PTH(1-34) will be measured using validated immunoassay with chemiluminescence detection technique .
Timepoint [3] 304090 0
Samples for estimation of PK profile of teriparatide will be drawn pre-dose (within 30 minutes prior to dosing), and post dose at 5, 10, 15, 20, 25, 30, 35, 40, 50 minutes and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, and 12 hours (Primary endpoint).
Secondary outcome [1] 340922 0
To evaluate safety and tolerability of Stelis Teriparatide [rh-PTH (1-34)] in comparison with the reference products Forsteo® (EU) and Forteo® (US) marketed by Eli Lilly. The safety assessment of injection site reactions will be done by visual observation.
Timepoint [1] 340922 0
Physical examination and injection site reactions will be done at the time of screening, on admission day in each period, 15 minutes prior to dosing and at 1, 2, 4, 6, 8, 10, 12 and 24 hours after dosing in each period and at the follow-up visit (Secondary endpoint).
Secondary outcome [2] 340924 0
Evaluate transient effects of Stelis Teriparatide [rh-PTH (1-34)] in comparison with the reference formulations Forsteo® (EU) and Forteo® (US) marketed by Eli Lilly, on baseline corrected ionized serum calcium. Ionized calcium concentration will be measured using a Radiometer ABL90 blood gas instrument.
Timepoint [2] 340924 0
Estimation of baseline corrected ionized serum calcium will be done at 0 hours (within 30 minutes prior to dosing), 1, 2, 3, 4, 6, 8, 12, and 24 hours post dose (Secondary endpoint).

Eligibility
Key inclusion criteria
1. Healthy male and non-pregnant female between the ages of 18- 45 years.
2. Body Mass Index of 18.5 to 28 kg/m2, and a minimum body weight of 50 kg at screening.
3. Female subjects of childbearing potential must practice effective contraception during the study and be willing and able to continue contraception for 30 days after their last dose of study treatment (Preferably two methods).
4. Must be non-smokers or ex-smokers who have not smoked within the previous 6 months from the screening visit.
5. Must be in general good health as determined by the Investigator based on comprehensive medical history, physical examination findings, vital sign measurements, and clinical laboratory tests, unless considered not clinically significant by the Investigator.
6. Ability to understand the purpose and risks of the study, and provide signed and dated study specific informed consent prior to any study-specific procedures.
7. Able and willing to participate in the study according to the protocol for the full length of expected term of follow-up
Minimum age
18 Years
Maximum age
45 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Known history of or positive test result for human immunodeficiency virus (HIV), hepatitis C virus [test for hepatitis C virus antibody (HCV Ab)], hepatitis B virus [test for hepatitis B surface antigen (HBsAg)], hepatitis B core antibody (HBcAb)] and/or Quantiferon Gold Blood Test.
2. History of severe allergic reactions to any drug or anaphylactic reactions.
3. Known allergy to Teriparatide or any other components of the product (both Test & Reference products).
4. History of Paget's disease of bone, active urolithiasis or primary hyperparathyroidism.
5. Preexisting hypercalcemia or unexplained elevations of alkaline phosphatase.
6. History of prior external beam or implant radiation therapy involving the skeleton.
7. Subjects with a history of malignant disease, including solid tumors and hematologic malignancies (except basal cell and squamous cell carcinomas of the skin that have been completely excised and are considered cured).
8. Has undergone major surgery within the previous 12 months from screening visit or is planning to undergo a major surgery within 12 weeks of screening visit.
9. Female subjects who are pregnant or have a positive pregnancy test result, currently breastfeeding, or planning to become pregnant during the course of the study.
10. Vaccinations within 4 weeks, prior to study medicine administration in period 1 and plan of any vaccination during the study or within 4 weeks after the completion of the study.
11. Blood donation (greater than equal to 500 mL) within 30 days prior to screening.
12. History of any clinically significant cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, or other major disease, as determined by the Investigator.
13. History of alcohol or substance abuse.
14. Positive result for drugs of abuse at screening or on admission to the study center including amphetamines, barbiturates, cocaine, methadone, 3, 4 methylenedioxymethamphetamine (ecstasy), phencyclidine, tetrahydrocannabinol, and opiates.
15. Use of any tobacco product (other than smoking) more than 5 times within 30 days prior to screening.
16. Positive testing for alcohol at screening or check-in.
17. Alcohol use within 48 hours prior to dosing on Day 1 of every period of the study. Subjects must be willing to restrict alcohol use throughout their participation in the study. Subjects may not consume more than 1 alcoholic beverage per day during the wash-out period of this study where 1 alcoholic beverage is defined as less than equal to 8 ounces of beer or less than equal to 4 ounces of wine.
18. Use of food or beverages such as grape fruit/ grapefruit juice, caffeine/xanthine-containing foods or beverages (like chocolate, tea, coffee or cola drinks) from 48 hours prior to dosing in each period and until after the last blood sample is collected.
19. Clinically significant abnormal clinical laboratory test values, as determined by the Investigator, or any values for alanine aminotransferase (ALT), aspartate aminotransferase (AST), or creatinine that are above the upper limit of normal, any values for platelets or hemoglobin that are below the lower limit of normal, or any out of normal range values for white blood cells, serum calcium, serum sodium, or serum potassium.
20. Clinically significant abnormalities in 12-lead ECG.
21. Any previous treatment with any parathormone/teriparatide product, including investigational use.
22. Prior treatment with any investigational drug within the 30 days prior to Day -1, or within 5 half-lives of the drug, whichever is longer.
23. Treatment with any medication prescribed or over-the-counter (OTC) products including analgesics, herbal remedies, calcium supplements, vitamin therapy (vitamins, minerals, and nutrition supplements may be taken at the discretion of the Investigator) within 14 days prior to Day -1 or longer if the medication has a long half-life, unless defined as not clinically significant by the Investigator and Sponsor. Exception: contraceptives.
24. Inability to comply with study requirements.
25. Ongoing or previous participation in another clinical trial within the previous 12 weeks before Day -1.
26. Other unspecified reasons that, in the opinion of the Investigator or sponsor, make the subject unsuitable for enrollment

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?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint/s
Pharmacokinetics / pharmacodynamics
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
3/02/2018
Actual
15/03/2018
Date of last participant enrolment
Anticipated
15/05/2018
Actual
24/05/2018
Date of last data collection
Anticipated
29/06/2018
Actual
15/06/2018
Sample size
Target
78
Accrual to date
Final
78
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 298109 0
Commercial sector/Industry
Name [1] 298109 0
Stelis Biopharma Private Limited
Country [1] 298109 0
India
Primary sponsor type
Commercial sector/Industry
Name
Stelis Biopharma Private Limited
Address
Stelis Biopharma Pvt. Ltd.
Plot no. 293, Bommasandra Jigani Link Road, Jigani Industrial Area, Anekal Taluk
Bangalore- 560105,INDIA
Country
India
Secondary sponsor category [1] 297187 0
Commercial sector/Industry
Name [1] 297187 0
Quintiles Pthy Ltd
Address [1] 297187 0
Quintiles Pty Ltd
Level 9, 67 Albert Ave
Chatswood NSW 2067
Australia
Country [1] 297187 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299128 0
Bellberry HREC
Ethics committee address [1] 299128 0
129 Glen Osmond Road
Eastwood South
Eastwood
Australia 5063
Ethics committee country [1] 299128 0
Australia
Date submitted for ethics approval [1] 299128 0
22/11/2017
Approval date [1] 299128 0
18/12/2017
Ethics approval number [1] 299128 0

Summary
Brief summary
Stelis Biopharma has developed a biosimilar formulation of Teriparatide which has been proven to be qualitatively comparable with approved product Forsteo® (EU) and Forteo® (US) being marketed by Eli Lilly through several analytical methods.
This Phase-1 study is designed to compare the pharmacokinetics, safety, tolerability, and pharmacodynamics of the biosimilar formulation developed by Stelis Biopharma with the reference formulation Forsteo® (EU) and Forteo® (US) being marketed by Eli Lilly and establish it's clinical comparability.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 79394 0
Dr Jason Lickliter
Address 79394 0
Nucleus Network Limited
Level 5 Burnet Institute
AMREP Precinct
89 Commercial Road
Melbourne 3004 Victoria
Country 79394 0
Australia
Phone 79394 0
+ 613 9076 8960
Fax 79394 0
Email 79394 0
[email protected]
Contact person for public queries
Name 79395 0
Durgaprasad Annavajjula
Address 79395 0
Stelis Biopharma Pvt. Ltd.
Plot no. 293, Bommasandra Jigani Link Road, Jigani Industrial Area, Anekal Taluk
Bangalore- 560105,INDIA
Country 79395 0
India
Phone 79395 0
+91 80 67840 444
Fax 79395 0
Email 79395 0
[email protected]
Contact person for scientific queries
Name 79396 0
Soumya Prakash Rout
Address 79396 0
Stelis Biopharma Pvt. Ltd.
Plot no. 293, Bommasandra Jigani Link Road, Jigani Industrial Area, Anekal Taluk
Bangalore- 560105,INDIA
Country 79396 0
India
Phone 79396 0
+91 80 67840 444
Fax 79396 0
Email 79396 0
[email protected]

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