A double blind single-dose study to evaluate pharmacokinetics, safety and tolerability of Stelis Teriparatide [rh-PTH (1-34)] with innovator product Forsteo Registered Trademark (European Innovator) in healthy volunteers via subcutaneous administration of a single dose of 20 mcg .

• Register: ANZCTR
• Last refreshed on: 13 January 2020
• Main ID: ACTRN12615000358549
• Date of registration: 20/04/2015
• Prospective Registration: Yes
• Primary sponsor: Stelis Biopharma Pvt. Ltd.
• Public title: A double blind single-dose study to evaluate pharmacokinetics, safety and tolerability of Stelis Teriparatide [rh-PTH (1-34)] with innovator product Forsteo Registered Trademark (European Innovator) in healthy volunteers via subcutaneous administration of a single dose of 20 mcg .
• Scientific title: A randomized, double blind, 2-treatment, 2-period, single-dose, cross over, comparative study to evaluate pharmacokinetics, safety and tolerability of Stelis Teriparatide [rh-PTH (1-34)] [teriparatide, Stelis Biopharma Pvt. Ltd., India] with ForsteoRegistered Trademark (teriparatide, Eli Lilly Nederland BV, Grootslag 1-5, NL-3991 RA Houten, The Netherlands) in healthy volunteers following subcutaneous administration of a single dose of 20 mcg Teriparatide
• Date of first enrolment: 16/10/2015
• Target sample size: 24
• Recruitment status: Completed
• URL: https://anzctr.org.au/ACTRN12615000358549.aspx
• Study type: Interventional
• Study design: Purpose: Treatment; Allocation: Randomised controlled trial; Masking: Blinded (masking used);Assignment: Crossover;Type of endpoint: Pharmacokinetics / pharmacodynamics;
• Phase: Phase 1

Countries of recruitment

Australia

Contacts

• Name: Dr Mohanlal Sayana

• Name: Dr Mohanlal Sayana

Key inclusion & exclusion criteria

Inclusion criteria: 1. Male or non-pregnant female between the ages of 18-45 years.
2. Body Mass Index of 19 to 30 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.
4. 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.
5. 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.
6. Able and willing to participate in the study according to the protocol for the full length of expected term of follow-up

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)] or hepatitis B virus [test for hepatitis B surface antigen (HBsAg)].
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. Subjects with a history of malignant disease, including solid tumors and hematologic malignancies (except basal cell and squamos cell carcinomas of the skin that have been completely excised and are considered cured).
5. 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.
6. 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.
7. Vaccinations within 4 weeks, prior to study medicine administration in period 1.
8. Blood donation (Greater than equal to 500 mL) within 30 days prior to screening.
9. 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.
10. History of alcohol or substance abuse.
11. Positive result for drugs of abuse on admission to the study center including amphetamines, barbiturates, cocaine, methadone, 3, 4 methylenedioxymethamphetamine (ecstasy), phencyclidine, tetrahydrocannabinol, and opiates.
12. Use of any tobacco product more than 5 times within 30 days prior to screening.
13. Positive testing for alcohol at check-in.
14. Alcohol use within 72 hours prior to dosing of period 01. Subjects must be willing to restrict alcohol use throughout their participation in the study.
15. 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 sodium, or serum potassium or as determined by the Investigator,
16. Clinically significant abnormalities in 12-lead ECG.
17. Any previous treatment with any parathormone/teriparatide product, including investigational use.
18. 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.
19. Treatment with any medication prescribed within 30 days prior to Day 1 or longer if the medication has a long half-life, and over-the-counter (OTC) products including analgesics, herbal remedies, vitamin therapy within 14 days prior to Day 1 or longer if the medication has a long half-life, unless agreed as not clinically significant by the Investigator (vitamins, minerals, and nutrition supplements may be taken at the discretion of the Investigator). Exception: contraceptives.
20. Inability to comply with study requirements.
21. Other unspecified reasons that, in the opinion of the Investigator or sponsor, make the subject unsuitable for enrollment.

Age minimum: 18 Years
Age maximum: 45 Years
Gender: Both males and females

Health Condition(s) or Problem(s) studied

Osteoporosis ;
Osteoporosis

Musculoskeletal - Osteoporosis

Intervention(s)

Test Product (T): Stelis Teriparatide [rh-PTH (1-34)] [teriparatide, Stelis Biopharma Pvt. Ltd., India]
Reference Product (R): Forsteo Registered Trademark (teriparatide, Eli Lilly Nederland BV, Grootslag 1-5, NL-3991 RA Houten, The Netherlands)
The volunteers will be administered 20 mcg Teriparatide from Test product or reference product through subcutaneous injection on either side of anterior abdominal wall, alternating between opposite sites in the 2 periods by trained nursing staff in accordance with the randomization scheme according to the instructions for medication administration of injection in pre-filled pen.

The Test product Stelis Teriparatide rhPTH(1-34) is formulated as a multi-dose (28 dose) small volume parenteral containing 250 mcg teriparatide (r-DNA origin) as active ingredient, 0.41 mg Glacial Acetic Acid as buffering agent, 0.10 mg Sodium Acetate (Anhydrous) as buffering agent, 45.4 mg Mannitol as tonicity modifier, 3.0 mg Metacresol as preservative, Hydrochloric Acid Solution 10% q.s. and Sodium Hydroxide Solution 10% q.s. for pH adjustment, Water for Injection q.s. 1 mL. The sterile finished product solution is aseptically filled into pre-sterile cartridges. The sealed cartridges are then finally assembled in the pen-injector. Stelis teriparatide biosimilar is thus identical in composition and strength to the innovator reference product FORSTEO (Registered Trademark). Stelis finished product also does not contain any ingredients of animal or human origin.

The Formulation Components, intended dosage and route of administration of Stelis Biosimilar Teriparatide is identical to the innovator reference product FORSTEO.
The comparability criteria for Stelis teriparatide biosimilar is established for the finished product via a q

Primary Outcome(s)

Cmax.

Plasma assay.[Samples for estimation of Teriparatide will be drawn pre-dose (within 30 minutes prior to dosing), and post dose at 5, 10, 20, 30, 40, 50 minutes and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10 and 12 hours.]

Primary parameters: AUC 0- inf.

Plasma assay. [Samples for estimation of Teriparatide will be drawn pre-dose (within 30 minutes prior to dosing), and post dose at 5, 10, 20, 30, 40, 50 minutes and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10 and 12 hours.]

Secondary Outcome(s)

Secondary parameter: time to Cmin (tmin).

Plasma Assay[Intact PTH (1-84) will be assessed at predose (duplicate),
and post dose at hours 0.5, 1, 2, 6 and 12.]

Secondary parameter: Observed and change from baseline ionized serum calcium concentrations.

Plasma Assay[In Period 1, Samples for estimation of ionised serum calcium will be drawn on Day -1 at -24, -23, -22, -20, -18, -16, -14, and -12 hours, to time-matched clock times scheduled for Day 1. On day 1 of both study periods samples for estimation of ionised serum calcium will be drawn pre-dose (within 30 minutes prior to dosing), and post dose at hours 1, 2, 4, 6, 8, 10, 12, 24 (Day 2).]

Secondary parameter: AUC0-t.

Plasma Assay[Samples for estimation of Teriparatide will be drawn pre-dose (within 30
minutes prior to dosing), and post dose at 5, 10, 20, 30, 40, 50 minutes
and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10 and 12 hours.]

Endogenous intact PTH(1-84) will be assessed at baseline and at times points 0.5, 1, 2, 6, and 12 hrs after dosing. The intact PTH(1-84) will be done by plasma assay using ELISA methods.[Intact PTH (1-84) will be assessed at predose (duplicate),
and post dose at hours 0.5, 1, 2, 6 and 12.]

Secondary parameter: Safety Endpoints: Local reaction incidence[The tolerability of the IP at local injection site will be assessed at 15 min prior to dosing and at 1, 2, 4, 6, 8, 10 12 and 24 hours after dosing in each period ]

Secondary parameter: Safety Endpoints: Incidence of grade 3-4 AEs[Incidence of grade 3-4 AEs will be monitored throughout the study. ]

Secondary parameter: T half.

Plasma assay[Samples for estimation of Teriparatide will be drawn pre-dose (within 30
minutes prior to dosing), and post dose at 5, 10, 20, 30, 40, 50 minutes
and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10 and 12 hours.]

Secondary parameter: Tmax

Plasma assay.[Samples for estimation of Teriparatide will be drawn pre-dose (within 30
minutes prior to dosing), and post dose at 5, 10, 20, 30, 40, 50 minutes
and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10 and 12 hours.]

Secondary parameter: Apparent clearance(CL/F).

Plasma assay[Samples for estimation of Teriparatide will be drawn pre-dose (within 30
minutes prior to dosing), and post dose at 5, 10, 20, 30, 40, 50 minutes
and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10 and 12 hours.]

Secondary parameter: Safety Endpoints: Adverse event (AE) and serious adverse event (SAE) incidence.
[Incidence of Adverse Events (AEs) and serious adverse event (SAE) will be monitored throughout the study. ]

Secondary parameter: Kel

Plasma Assay[Samples for estimation of Teriparatide will be drawn pre-dose (within 30
minutes prior to dosing), and post dose at 5, 10, 20, 30, 40, 50 minutes
and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10 and 12 hours.]

Secondary parameter: Safety Endpoints: Incidence of anti-teriparatide antibodies[The Incidence of anti-teriparatide antibodies will be assessed at day 1(prior to dosing) and at days 7 (+/- 1), 14 (+/- 1) and 28 days after dosing in each period. ]

Secondary parameter: Apparent volume of distribution(Vz/F).

Plasma assay. [Samples for estimation of Teriparatide will be drawn pre-dose (within 30
minutes prior to dosing), and post dose at 5, 10, 20, 30, 40, 50 minutes
and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10 and 12 hours.]

Secondary ID(s)

Nil

Source(s) of Monetary Support

Stelis Biopharma Pvt. Ltd.

Ethics review

Status: Approved
Approval date:
Contact:

The Alfred Health Human Ethics Commitee