Multicenter randomized single dose parallel open label bioequivalence
- Conditions
- Other acquired hemolytic anemias,
- Registration Number
- CTRI/2022/11/047535
- Lead Sponsor
- Emcure Pharmaceuticals Limited
- Brief Summary
It is a multicenter, randomized, single dose, parallel, two treatment, comparative, open label, bioequivalence study of Ferric Carboxymaltose Injection, 50 mg/ml (750mg/15ml) of Emcure Pharmaceutical Limited, with INJECTAFER® (ferric carboxymaltose injection), 750 mg iron/15ml of American Reagent, Inc., in adult patients with iron deficiency anemia, for whom oral supplementation alone was not adequate or is not appropriate. 22 adult male and female patients will be randomized to get 18 evaluable subjects.
Patients will be housed at least 36.00 hours prior to drug dosing and until at least 168.00 hours after dosing.
**Primary objective:**To assess the bioequivalence of Ferric Carboxymaltose Injection 50 mg/ml (750mg/15ml) of Emcure Pharmaceutical Limited with INJECTAFER® (ferric carboxymaltose injection) of American Reagent, Inc., 750 mg iron/15ml, to adult patients with iron deficiency anemia.
**Secondary objective:**To assess the safety and tolerability of Emcure’s Ferric Carboxymaltose Injection 50 mg/ml (750mg/15ml) with INJECTAFER® (ferric carboxymaltose injection), 750 mg iron/15ml based upon reported adverse events, clinical laboratory results, clinical investigations, and vital signs.
Blood samples will be collected prior to dosing and for 168.00 hours after drug dosing.
**Inclusion Criteria**:1. All patients should be judged by the Principal Investigator or Medical Sub-Investigator as normal and relatively healthy (excluding iron-deficiency anemia) during a pre-study medical evaluation performed within 28 days of the initial dose of study medication which will include:
a. A normal or clinically non- significant physical examination, including vital signs (blood pressure, pulse rate, respiratory rate and temperature). Acceptable range for vital signs is as follows:
1. Systolic blood pressure between 100-140 mmHg and diastolic blood pressure 60-90 mmHg.
2. Pulse rate 60-100 bpm, respiratory rate 12-20 breaths per minute.
3. Axillary temperature 96.0–99.0°F.
During screening, vital signs may be repeated once (unless otherwise specified). If the repeat measurement remains outside of the acceptable range, the Principal Investigator or Medical Sub-Investigator will determine the appropriate course of action. If the subject is permitted to enter the study, then written justification is required.
b. Within normal limits or clinically non-significant laboratory evaluation results for the following tests (unless otherwise noted below or in the Exclusion Criteria):
*Serum Chemistries*
| | | | |
| --- | --- | --- | --- |
|Sodium
Potassium
Chloride
BUN
|Prothrombin time
Albumin
Total Protein
AST
|Alkaline Phosphatase
Calcium
Creatinine
ALT
|Total Bilirubin
Total Cholesterol\*
Phosphate
|Uric Acid
Glucose\*
Triglycerides\*
\*Fasting or non-fasting may be performed based on clinical judgment
i. AST and ALT ≤ 3 times ULN,
ii. Alkaline phosphatase ≤ 2.5 times ULN,
iii. Bilirubin ≤ 1.5 times ULN
· Haematology
Platelet Count White Blood Cell Count WBC /Differential
Haemoglobin Haematocrit Red Blood Cell Count
i. Haemoglobin of < 12g/dL at screening
ii. ANC ≥ 1500/mm3
iii. Platelet count ≥ 100,000/mm3
Urinalysis : 1 . Appearance
2. Specific Gravity
3. Protein
4. pH
5. Microscopic Examination (performed based on clinical judgment)
2. Additional tests may be performed, if necessary, based on standard lab panels utilized by the clinical site.
3. Normal or clinically nonsignificant 12-lead ECG.
4. Negative Hepatitis B antigen test.
5. Negative Hepatitis C antibody test.
6. Negative HIV test.
7. Negative chest X-ray for tuberculosis. A negative chest X-ray acquired within 6 months of study start and having adequate documentation available is acceptable at the discretion of the Principal Investigator or responsible physician.
8. Tests for other sexually transmitted diseases (STD) may be performed at the discretion of the Principal Investigator or responsible physician,
9. Negative urine drug screen including at a minimum amphetamines, barbiturates, benzodiazepines, cannabinoid, cocaine, and opiates.
Note: If warranted, other tests and/or examinations may be performed at the discretion of the Principal Investigator or responsible physician to determine patient eligibility. Any additional tests used to confirm patient’s eligibility are to be included in the patient’s CRF.
The schedule of the patient’s visit at study site will be as follows:
-Screening visit**(-28 days)**
**-Day (-2) (Check in -36.00 hours)**
**-Day (-1) (-24.00 hours)**
**-Days 1 to Day 4 (In house treatment period)**
**-Day 4 (Check-out 168.00 hours)**
-End of Study/ Safety follow-up visit
**Exclusion Criteria:**
1. Diseases:a) History of any significant cardiovascular, hepatic, renal, pulmonary, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, psychological, genitourinary, musculoskeletal disease or malignancies unless deemed clinically non-significant by the Principal Investigator or Medical Sub-Investigator.
b) Patients with known active malignancy (i.e., clinical evidence of current malignancy or not in stable remission for at least 5 years since completion of last treatment with exception of basal cell or squamous cell carcinoma of the skin, and cervical intraepithelial neoplasia). Blood loss leading to hemodynamic instability.
c) History of tuberculosis.
d) Glomerular Filtration Rate (GFR) less than 60 ml/min as estimated by using the
Cockcroft-Gault equation.
Males: CLCr = [140-age(years) x weight(kg)] / 72x serum creatinine(mg/dl)
Females: CLCr= [140-age(years) x weight( kg) x 0.85 / 72 x serum creatinine(mg/dl)
2.Patients with clinically significant or labile hypertension.
f) 3. Patients with significant comorbidities such as congestive heart failure, asthma, decompensated liver cirrhosis, eczema or atopic allergy, acute/chronic infection of any type, systemic lupus erythematous, rheumatoid or inflammatory arthritis, inflammatory bowel disease, rheumatic disease or any other condition, that in the investigator’s judgment, might increase the risk to the patient or decrease the chance of obtaining satisfactory PK data.
g) 4.Acute illness at the time of either the pre-study medical evaluation or at the time of dosing.
1. Donation or loss of blood or plasma: 50 mL or more within 90 days prior to the administration of study medication.
2. Patients who have received an investigational drug within 90 days prior to the administration of study medication.
3. Any food allergy, intolerance, restriction or special diet that, in the opinion of the Principal Investigator or Medical Sub-Investigator, could contraindicate the patient’s participation in this study.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Not Yet Recruiting
- Sex
- All
- Target Recruitment
- 22
- 1.Patients diagnosed with iron deficiency anemia, for whom oral supplementation alone is not adequate/appropriate. 2.Iron status evaluation (Total Iron Binding capacity, Serum Iron ≤ 10 mmol, % Transferrin Saturation, Serum Ferritin ≤ 100ng/mL or ≤300ng/mL when TSAT is ≤30%. Observed values for Total Iron Binding Capacity, %Transferrin Saturation and Serum Ferritin are to be consistent with a primary diagnosis of iron deficiency anemia. 3.Age, race, & ethnicity: Adults between the ages of 18 and 65 years. Patient must meet age requirements at the time of signing the initial informed consent and at the time of study drug administration. In addition, the patient’s race (e.g. Caucasian, Black, Asian, etc) and ethnicity (i.e. Hispanic, Non-Hispanic) should be documented. 4.Sex: Males and/or non-pregnant, non-lactating females. a.Women of childbearing potential must have a negative serum beta human chorionic gonadotropin (β-HCG) pregnancy test performed within 28 days prior to the initial dose of study medication. b.Women taking hormone replacement therapy or receiving a hormonal contraceptive will be eligible to participate as long as they have been on a stable regimen for at least 3 months prior to receiving the study medication and plan to remain on the same regimen for the duration of this study or women using an intrauterine device for at least 3 months prior to receiving the study medication. c.Women will not be considered of childbearing potential if one of the following is reported and documented on the medical history: i.Postmenopausal with spontaneous amenorrhea for at least one (1) year, or spontaneous amenorrhea for less than one (1) year with serum FSH levels >40mIU/ml, or ii.Bilateral oophorectomy with or without a hysterectomy and an absence of bleeding for at least 6 months, or iii.Total hysterectomy and an absence of bleeding for at least 3 months. 5.Weight: Each patient is required to weigh at least 50 kg. 6.Body Mass Index (BMI) should be between 18.5 kg/m2.
- 30.0 kg/m2. (both inclusive) 7.Smoking Status: Non-smokers preferred, however, up to moderate smokers (up to 10 cigarettes and biddies or equivalent per day with results included in the study database (if applicable), and Patient’s CRF. 8.Adequate venous access in both arms for the collection of a number of blood samples during the study. 9.Able to understand & give written informed consent. Utilization of only literate patients are permitted 10.Willing to follow the protocol requirements and comply with protocol restrictions.
- 1.Hospitalised patients i.e. the patients who are currently hospitalised.
- 2.Social Habits: a)Ingestion of any alcoholic beverage within the 48.00 hours prior to the initial administration of study medication.
- b)Ingestion of any caffeine- or xanthine-containing food or beverage within the 24.00 hours prior to the initial administration of study medication.
- c)Ingestion of any vitamins or herbal products within 7 days prior to the initial administration of the study medication.
- d)Any recent, significant change in dietary or exercise habits.
- f)Use of any nicotine containing product during any in-house study period.
- 3.Medications: a)Parenteral iron therapy within 6 months prior to the initial dose of study medication.
- b)Oral iron therapy within 14 days prior to randomization.
- c)Erythropoiesis stimulating agents within 3 months prior to the initial dose of study medication.
- d)Patients receiving concomitant medications (e.g. iron chelating agents such as deferoxamine, deferasirox, deferiprone, deferitazole, zinc picolinate, chromium picolinate etc.) that affect the pharmacokinetics of iron may be excluded following consultation with a pharmacokinetic team.
- 4.Patients with hemochromatosis or other iron storage disorders.
- 5.Patients who had major surgery or invasive intervention within 4 weeks prior to screening, organ transplant within 6 months prior to screening, or have a surgery or intervention planned during the course of the study.
- 6.Patients who received a whole blood transfusion or red blood cell transfusion within 90 days prior to the administration of study medication.
- 7.Any reason which, in the opinion of the Principal Investigator or Medical Sub-Investigator, would prevent the patient from safely participating in the study.
- 8.Intolerance to venipuncture.
Study & Design
- Study Type
- BA/BE
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To assess the bioequivalence of Ferric Carboxymaltose Injection 50 mg/ml (750mg/15ml) of Emcure Pharmaceutical Limited with INJECTAFER® (ferric carboxymaltose injection) of American Reagent, Inc., 750 mg iron/15ml, to adult patients with iron deficiency anemia. Screening | (-28 days)Day (-2) (Check in -36.00 hours)Day (-1) (-24.00 hours)Days 1 to Day 4 (In house treatment period)Day 4 (Check-out 168.00 hours)End of Study/ Safety follow-up visit
- Secondary Outcome Measures
Name Time Method To assess the safety and tolerability of Emcure’s Ferric Carboxymaltose Injection 50 mg/ml (750mg/15ml) with INJECTAFER® (ferric carboxymaltose injection), 750 mg iron/15ml based upon reported adverse events, clinical laboratory results, clinical investigations, and vital signs.
Trial Locations
- Locations (5)
Care Hospital
🇮🇳Agra, UTTAR PRADESH, India
Divine Multispeciality Hospital
🇮🇳Gandhinagar, GUJARAT, India
Jupiter Hospitals & research centre
🇮🇳Vadodara, GUJARAT, India
Lakeview Goaves Heart & Muli Super Specialty Hospital
🇮🇳Belgaum, KARNATAKA, India
Medstar Speciality Hospital
🇮🇳Bangalore, KARNATAKA, India
Care Hospital🇮🇳Agra, UTTAR PRADESH, IndiaDr Prabhatkumar AgrawalPrincipal investigator9319250485ppagrawal120@gmail.com