An Open Label, Randomized, Balanced, Two-treatment, Single Period, Parallel, Single Dose, Subcutaneous Administration, Comparative Pharmacokinetic Study Under Fasting Conditions.
An Open Label, Randomized, Balanced, Two-treatment, Single Period, Parallel, Single Dose, Subcutaneous Administration, Comparative Pharmacokinetic Study Under Fasting Conditions.
The Goal of these study is to evaluate and To compare the pharmacokinetics (PK) of the Test product (T) getting administered through prefilled syringe with on-body injector with Reference product as prefilled syringe following a single 6 mg dose administered through subcutaneous route in healthy adult Human subjects.
Subjects safety and immunogenicity will also be evaluated during these study as follows Safety - monitoring the adverse events , vitals signs, ECG, laboratory parameters, and injection site assessment.
Immunogenicity assessment- detection of ADA (Anti-PEG antibody levels ) and Nab (Neutralizing antibodies) will be done pre-dose and post dose on day 15 of each period.
An Open label, randomized, single-dose, two sequences, two-period crossover comparative Pharmacokinetic, immunogenicity and safety study under fasting conditions. Duration of the clinical phase will be approximately 51 days starting from admission of period I until giving the last sample in period II.
A washout period of at least 34 days will be kept between dosing day in period I and dosing day period II.
Approximate volume of blood loss in the study will be 309 mL for both male and female's subjects. A total of Twenty-two (22) blood samples for PK parameters will be collected in SST tubes in each study period. Blood samples (5.0 mL) will be collected at pre-dose (00.00 hr) in the morning of dosing day (day 1) within 01.00 hour prior to dosing and at 00.33, 00.50, 00.75, 01.00, 02.00, 04.00, 06.00, 08.00, 10.00, 12.00,14.00, 16.00, 20.00, 24.00 (day 2), 36.00, 48.00 (day 3), 72.00 (day 4), 120.00 (day 6), 192.00 (day 9), 264.00 (day 12), 336.00 (day 15) hours post-dose during each study period.
Immunogenicity samples for ADA detection (anti-PEG- antibody) and Nab (Neutralizing antibodies) will be collected at pre- dose, and on day 15 (4.0 mL for each sampling time/ test) during each study period, into SST tubes.
Summary Statistics will be calculated for Pegfilgrastim pharmacokinetic parameters Cmax, AUC0-t and AUC0-inf, Tmax, t12, Kel and AUC Extrapolated. Statistical tests like ANOVA, least square means for test and reference products, Two One- Sided Tests for 90% confidence interval limits and power will be calculated for In-transformed pharmacokinetic parameters Cmax, AUC0-t and AUC0-inf Geometric least square means of test and reference products, it's ratio, 90% confidence interval for geometric least square means ratio and intra-subject variability will be calculated for pharmacokinetic parameters Cmax, AUC0-t and AUC0-inf for Pegfilgrastim.
Dose normalization for Cmax, AUC0-t and AUC0-inf will be done considering the actual administered dose for each subject (based on the difference in PFS/OBI/AI weight before and after dosing). This is an additional PK analysis dataset.
Inclusion Criteria:
The subject's Liver function tests (AST, ALT, GGT, and total bilirubin) results are within the medical lab reference ranges and liver function tests (Alkaline phosphatase, total protein, and albumin) are considered clinically acceptable as per PI / SI judgment at screening.
7.The subject's Cholesterol level is considered clinically acceptable as per PI / SI judgment at screening.
8.The subject is fasting for at least 12 hrs before giving the samples required for clinical laboratory examinations as checked at screening .
9.Subject having vital signs parameters (blood pressure, body temperature, pulse rate and respiratory rate) are within the following ranges at screening, and on admission day (before admission) of period I: Blood Pressure: Systolic: (90- 140) mmHg, Diastolic: (60-90) mmHg Body Temperature: (36.1 - 37.2) ºC Pulse rate: 60 to 100 beat per minute. Respiratory rate: 12-18 bpm. 10.Subject complies with Injection site evaluation at screening and on admission day (before admission) of period I.
11.The subject has a normal ECG (12 leads) as per the investigator judgement, at screening and on admission day (before admission) of period I.
12.The subject has normal abdominal ultrasonography (no signs of spleen rupture or splenomegaly) as checked at screening 13.The subject has clinically acceptable chest x-ray (PA view) as per the investigator judgment as checked at screening.
14.The subject has having negative urine screen for drugs of abuse (amphetamine, barbiturates, benzodiazepines, cocaine, opiates, marijuana, methadone, methamphetamine, phencyclidine, and Tricyclic antidepressants) at screening and on admission day (before admission) of period I .
15.The subject has negative alcohol test at screening and on admission day (before admission) of period I.
16.The subject (available for entire study duration) is willing to adhere to the protocol requirements and to provide signed informed consent (by applying his / her signature or fingerprint) as confirmed at screening and on admission day (before admission) of period I.
Females of non-childbearing potential must have undergone sterilization procedures, at least 6 months prior to the first dose or be postmenopausal with amenorrhea for at least 1 year prior to the first dose and follicle-stimulating hormone (FSH) serum levels consistent with postmenopausal status 18.For Female Subjects "who have the potential to become pregnant":
•The subject has negative serum pregnancy test at screening and on admission day (before admission) of period I.
Female of child bearing potential agrees to practice for the duration of the study an acceptable method of birth control as judged by the investigator(s), such as intrauterine device (IUD), abstinence or double barrier contraception, i.e., condom + diaphragm, condom + spermicidal or foam prior to the start of the study and through the study and for 30 days after last dosing in study as checked at screening and on admission day (before admission) of period I.
19.The male subject agrees, at screening and on admission day (before admission) of period I, to use a condom for the duration of the study, and for 30 days after last dosing in study if: He is engaged in sexual activity with a woman of childbearing potential.
A condom is required along with another medically acceptable contraceptive method. Medically acceptable methods of contraception include non-hormonal intrauterine device or double barrier method (condom with foam or vaginal spermicidal suppository, diaphragm with spermicide).
Not to donate sperms during the study and for 30 days after last dosing in study
Exclusion Criteria:
Subjects will be excluded from the study, if they meet any one of the following criteria:
Splenic Rupture or Splenomegaly. Acute respiratory distress syndrome Sickle Cell Disorders Glomerulonephritis Leukocytosis Thrombocytopenia Capillary Leak Syndrome History of cancer; or malignant Cells. Aortitis History of pulmonary infiltrate or pneumonia (radiologically confirmed) within 6 months prior to initial dosing.
Any past exposure to recombinant human G-CSF products and/or a known history of prior treatment with blood-cell colony stimulating factors, interleukins or interferons.
History or presence of asthma, urticaria or other significant allergic reactions as checked at screening.
7.History or presence of significant gastric and/or duodenal ulceration as checked at screening.
8.The subject has received any vaccination (including influenza) within 60 days prior to first dosing as checked at screening.
9.The subject used any treatment which could bring about induction or inhibition of hepatic microsomal enzyme system within 1 month prior to dosing of Period I as checked at screening or on admission day (before admission) of period I.
10.The subject is a moderate smoker (more than 10 cigarettes per day) as checked at screening or on admission day (before admission) of period I 11.History or presence of drug abuse in the past one year as checked at screening.
12.History or presence of alcohol abuse in the past one year [alcohol abuse will be >14 drinks per week (1 drink = 360 mL beer, 150 mL wine, or 45 mL hard liquor)] as checked at screening.
13.Difficulty with donating blood as checked at screening or on admission day (before admission) of period I.
14.Use of any prescribed medication or OTC medication including vitamins and herbal remedies during last 14 days prior to dosing in period I as checked at screening or on admission day (before admission) of period I.
15.Major illness or hospitalization within past 3 months as checked at screening or on admission day (before admission) of period I.
16.Volunteer/s who have donated 1 unit blood (≥ 300 mL) or participated in a clinical study involving blood sampling within 80 days prior to the first dose of the study drug as checked at screening or on admission day (before admission) of period I.
17.Consumption of grapefruit juice, caffeine, poppy seeds, within 72 hours prior to dosing and other xanthine-containing products, tobacco containing products or any alcoholic products within 48 hours prior to dosing as checked on admission day (before admission) of period I .
18.Positive test for one or more: HIV, Hepatitis B and Hepatitis C at screening.
19.History or presence of significant easy bruising or bleeding as checked at screening.
History or presence of significant recent trauma as checked at screening. 21.Female volunteer who has used implanted or injected hormonal contraceptives anytime during the 6 months prior to study or used hormonal contraceptives within 14 days before dosing as checked at screening or on admission day (before admission) of period I.
22.Female subjects who are currently breast feeding as checked at screening or on admission day (before admission) of period I.
23.Pregnant female volunteers as checked at screening or on admission day (before admission) of period I.
24.Known allergies to acrylics (as the on-body injector uses acrylic adhesive) as checked at screening or on admission day (before admission) of period I.