A Study of INTG8 in Healthy Men and Postmenopausal Women

Phase 1

Not yet recruiting

Conditions: HEALTHY MEN AND POSTMENOPAUSAL WOMEN

Registration Number: CTRI/2018/09/015697

Lead Sponsor: INTAS PHARMACEUTICALS LIMITED

Brief Summary: The present study has been designed to establish pharmacokinetic bioequivalence and compare pharmacodynamic profiles of INTG8 of Intas Pharmaceuticals Limited, India against Forteo (Lilly USA, LLC) and Forsteo (ELI LILLY NEDERLAND B.V., THE NETHERLANDS) following single subcutaneous injection of 20 micro gram in healthy men and postmenopausal women under fasting condition. This is an assessor-blind, randomized, three-treatment, three-period, single-dose, crossover, bioequivalence study in healthy men and postmenopausal women after subcutaneous administration under fasting conditions. Sufficient number of healthy men and postmenopausal women subjects meeting the inclusion and exclusion criteria will be enrolled in comparable manner to ensure that total 99 healthy men and postmenopausal women are randomized and the clinical data is statistically acceptable. At least a 24-hour washout will be given between two periods. Participation in this study yields no direct benefit to the subjects. The risk of common adverse reaction (nausea, pain in limb, headache, dizziness) and hypersensitivity are reduced considering the fact that only three doses are to be administered at an interval of not less than 01day (i.e. 24 hours) between the dosing days of two consecutive periods. No additional tests apart from the already specified (unless required for safety reasons in opinion of the PI) will be performed. The study will therefore not put any additional risk / burden to the subjects. Subjects will be on an overnight fast for at least 10 hours prior to dose administration and for 4 hours post dose administration. Each subject will receive dose of 20 micro gram (either of Test product or Reference products) subcutaneously on the abdomen in supine posture in each period. Subjects will be housed in the clinical facility for at least 11 hours before administration of the first dose (Period-I) and will continue to remain in the clinical facility till the end of Period III. A total of 48 blood samples (each of 3 mL) for pharmacokinetics evaluation and 36 blood samples (each of 2 mL) for pharmacodynamic evaluation will be collected in entire study. Subject will be instructed not to participate in other clinical trial or donate blood anywhere else during the study. The trial will be conducted in accordance with the protocol and will comply with all requirements regarding the obligations of investigators and all other pertinent requirements of ICH E6 (R2) â€˜Guideline on Good Clinical Practiceâ€™, 2016. The results of the study including all obtained data will be property of the sponsor.

Detailed Description: Not available

Recruitment & Eligibility

Status: Not Yet Recruiting

Sex: All

Target Recruitment: 99

Inclusion Criteria

Non-smokers, Non-tobacco users, normal, healthy, adult, human male subjects between 18 and 45 years of age (both inclusive) and postmenopausal women subjects between 45 and 65 years of age (both inclusive) 2.
Having a Body Mass Index (BMI) between 18.5 to 30 (both inclusive), calculated as weight in kg per height in meter square 3.
Postmenopausal women with serum FSH levels greater than 40 mIU per mL: Postmenopausal women includes women with 6 months of spontaneous amenorrhea or 6-week post-surgical bilateral oophorectomy with or without hysterectomy prior to the start of the study (Investigator may request the official report to confirm the surgery date and exclude cancer as the cause needing surgery).
Able to comply with the study procedures, in the opinion of the Principal Investigator.
Able to give voluntary written informed consent for participation in the trial.
Serum pregnancy test at the time of screening must be negative (for females).

Exclusion Criteria

Known hypersensitivity or idiosyncratic reaction to teriparatide or any related drug.
Subjects with known latex allergies.
Subjects will be assessed for orthostatic hypotension (Defined as decrease in systolic blood pressure of 20 mm Hg or a decrease in diastolic blood pressure of 10 mm Hg within 3 minutes of standing when compared with blood pressure from sitting or supine position) and confirmed unsafe for study inclusion by the investigator.
Subjects with systemic hypotension (Below 90 mm Hg systolic blood pressure in sitting position) and considered unfit for trial by the investigator.
History or presence of any disease or disorder known to influence bone metabolism, compromise the haemopoietic, renal, hepatic, endocrine, pulmonary, central nervous, cardiovascular, immunological, dermatological, gastrointestinal or any other body system.
History or presence of metabolic bone disease, active or recent urolithiasis, hypercalcemia and hypercalcaemic disorders, osteosarcoma or Pagetâ€™s disease of bone, prior external beam or implant radiation therapy involving the skeleton.
Subjects with history of ingestion of medicine (including herbal remedies) at any time within 14 days prior to dosing in period-I.
In any such case, subject selection will be at the discretion of the Principal Investigator.
Any history or presence of asthma (including aspirin-induced asthma) or nasal polyp or NSAID-induced urticaria.
A recent history of harmful use of alcohol (less than 2 years), i.e., alcohol consumption of more than 7 standard drinks per week (A standard drink is defined as 360 mL of beer or 150 mL of wine or 45 mL of 40 percentage distilled spirits, such as rum, whisky, brandy, etc.) or consumption of alcohol or alcoholic products within 48 hours prior to receiving the study drug.
Smokers or tobacco users, who consumed tobacco or tobacco-containing products (gutkha, pan/pan masala, beedi, cigarettes, others) within 6 months prior to start of the study or has inability to abstain from smoking during the study period.
Having any significant diseases or clinically significant abnormal findings during screening, medical history, clinical examination, laboratory evaluations, 12-lead ECG, Abdominal-pelvis ultrasonography (for females only) and X-ray chest (postero-anterior view) recordings.
Use of any recreational drugs or history of drug addiction or testing positive in pre-study drug scans.
History or presence of psychiatric disorders.
A history of difficulty with donating blood.
Donation of blood (1 unit or 350 mL) or receipt of an investigational drug or product or participation in a drug research study within 6 months prior to receiving the first dose of the study medicine.
A positive hepatitis screen including hepatitis B surface antigen and/or HCV antibodies.
A positive test result for HIV(I and II) antibody.
Consumption of grape fruit or grape fruit products within 72 hours prior to dosing.
Male subject with hemoglobin level less than 11.1 gm/dL and female subjects with hemoglobin level less than 10 gm/dL.
Subjects with abnormal PTH level, i.e., PTH level less than 15 pg/mL or greater than 65 pg/mL.
An unusual diet (e.g., low-sodium) for 4 weeks prior to receiving the study medicine.
Nursing mothers (For females).
Previous treatment, including for investigational purposes, with human parathyroid hormone OR any products derived from human parathyroid hormone.
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).

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Pharmacokinetic bioequivalence of INTG8 of Intas Pharmaceuticals Limited, India against Forteo (Lilly USA, LLC) and Forsteo (ELI LILLY NEDERLAND B.V., THE NETHERLANDS)	(0.000 and at 0.083, 0.167, 0.250, 0.333, 0.500, 0.750, 1.000, 1.333, 1.667, 2.000, 2.500, 3.000, 4.000, 5.000, 6.000 hour post dose

Secondary Outcome Measures

Name	Time	Method
-Assessment and comparision of local tolerance, safety and tolerability of INTG8 of Intas Pharmaceuticals Limited, India against Forteo (Lilly USA, LLC) and Forsteo (ELI LILLY NEDERLAND B.V., THE NETHERLANDS)	-Assessment and comparision of pharmacodynamics of INTG8 of Intas Pharmaceuticals Limited, India against Forteo (Lilly USA, LLC) and Forsteo (ELI LILLY NEDERLAND B.V., THE NETHERLANDS)

Trial Locations

Locations (1): Lambda Therapeutic Research Ltd
🇮🇳
Ahmadabad, GUJARAT, India
Lambda Therapeutic Research Ltd
🇮🇳Ahmadabad, GUJARAT, India
Dr Anshul Attrey
Principal investigator
07940202274
anshulattrey@lambda-cro.com