Bioequivalence Study of Tacrolimus in Healthy Volunteers

Completed · Phase 1

Conditions studied: Healthy Volunteers

In brief

This is an in-vivo study to investigate the bioequivalence of generic tacrolimus and its reference listed drug (RLD). The objective of this study is to investigate the bioequivalence of generic Tacrolimus and RLD in healthy male and non-pregnant, non-lactating female volunteers under fasting conditions. The outcome of this study will help further understanding about pharmacokinetic (PK) performance of tacrolimus in a healthy volunteer population and improve review standards for bioequivalence of narrow therapeutic index (NTI) drugs.

Key facts

Study ID

NCT04725682

Run by

Food and Drug Administration (FDA)

People needed

67

Starts

2021-01-05

Expected to finish

2021-06-17

Last updated by the study team

2023-09-21

Who can join

Age: 18 and older, up to 59. Sex: any. Healthy volunteers: accepted.

You may qualify if…

• Males and female volunteers, 18 -59 years of age (inclusive).
• BMI that is within 18.5-33.0 kg/m², inclusive.
• Healthy, according to medical history, ECG, vital signs, laboratory results and physical examination as determined by the PI/Sub-Investigator.
• Capable of giving written informed consent prior to receiving any study medication.
• Availability to volunteer for the entire study duration and willing to adhere to all protocol requirements.
• Smokers: Capable of refraining from smoking for the duration of the confinement.
• Female subjects must be non-pregnant, non-lactating and fulfill at least one of the following:
• Be surgically sterile for a minimum of 6 months
• Post-menopausal for a minimum of 12 months; Menopause defined as 12 months of amenorrhea without any other obvious pathological or physiological cause.
• Agree to avoid pregnancy and use medically acceptable method of contraception from at least 30 days prior to the study until 30 days after the study has ended (last study procedure).
• Medically acceptable methods of contraception include non-hormonal intrauterine device or double barrier method (foam or vaginal spermicidal suppository in conjunction with a male condom, diaphragm with spermicide in conjunction with a male condom). Abstinence as a method of contraception is acceptable if it is in line with the preferred and usual lifestyle of the study participant.
• If a female subject becomes pregnant during participation in the study or within 30 days after she has completed her last tacrolimus administration (whichever was administered last), she must inform BPSUSA staff immediately.
• Males who are able to father children must agree to use medically acceptable methods of contraception and not to donate sperm during the study and for 30 days after the end of the study.
• Medically acceptable methods of contraception include using a condom with a female partner of child-bearing potential who is using: oral contraceptives, hormonal patch, implant or injection, intrauterine device, or diaphragm with spermicide.
• If a male subject's partner becomes pregnant during his participation in the study or within 30 days after he has completed his last tacrolimus administration (whichever was administered last), he must inform BPSUSA staff immediately.

You may not qualify if…

• Known history and/or presence of any clinically significant hepatic (e.g., hepatitis, jaundice, hepatic failure, hepatic necrosis, hepatic encephalopathy, biliary tract diseases, cirrhosis), renal/genitourinary (e.g., urethral stricture, any renal impairment), gastrointestinal, cardiovascular (e.g., hypotension including orthostatic hypotension, cor pulmonale, congenital long QT, congestive heart failure, bradyarrhythmias), cerebrovascular, pulmonary (e.g., chronic obstructive pulmonary disease, decreased respiratory reserve, hypoxia, pre-existing respiratory depression), endocrine (e.g., myxedema, hypothyroidism, adrenal cortical insufficiency), immunological, musculoskeletal (e.g., kyphoscoliosis), neurological (e.g., CNS depression or coma, increased cerebrospinal pressure), psychiatric (e.g., psychosis, depression, hallucinations, delirium tremens, suicidal thoughts or behavior), dermatological or hematological (e.g., thrombocytopenic purpura) disease or condition unless determined as not clinically significant by the PI/Sub- Investigator.
• History or presence of any clinically significant gastrointestinal pathology (e.g., chronic diarrhea, inflammatory bowel disease), unresolved gastrointestinal symptoms (e.g., diarrhea, vomiting), or other conditions known to interfere with the absorption, distribution, metabolism or excretion of the drug experienced within 7 days prior to first tacrolimus administration, as determined by the PI/Sub-Investigator.
• Systolic blood pressure outside 90-130 mmHg, inclusive, and diastolic blood pressure outside 55-80 mmHg, inclusive, and heart rate between 50-100 bpm, inclusive, unless deemed otherwise by the PI/Sub-Investigator.
• QTc interval ≥ 440 milliseconds for males and ≥ 460 milliseconds for females, unless deemed otherwise by the PI/Sub-Investigator.
• Abnormal clinical laboratory values unless values are deemed by the PI/Sub- Investigator as "Not Clinically Significant".
• Abnormal vital signs (blood pressure [BP], heart rate [HR], respiratory rate [RR], pulse oximetry and temperature) measurements, unless deemed otherwise by the PI/Sub-Investigator.
• Presence of any clinically significant illness within 30 days prior to first dosing, as determined by the PI/Sub-Investigator.
• Presence of any significant physical or organ abnormality as determined by the PI/Sub-Investigator.
• A positive test result for any of the following: HIV, Hepatitis B surface antigen, Hepatitis C, drugs of abuse (marijuana, amphetamines, barbiturates, cocaine, opiates, phencyclidine and benzodiazepines), and alcohol test. Positive serum or urine pregnancy test for female subjects.
• Known history or presence of:
• Alcohol abuse or dependence within one year prior to first study drug administration;
• Drug abuse or dependence;
• Hypersensitivity or idiosyncratic reaction to tacrolimus, its excipients, and/or related substances;
• Lymphoma and other malignancies (particularly of the skin);
• Bacterial, viral, fungal and protozoal infections (e.g., polyoma virus- associated nephropathy [PVAN] due to BK virus infection, JC virus associated progressive multifocal leukoencephalopathy [PML], Epstein Barr Virus (EBC) associated Post transplant lymphoproliferative disorder [PTLD], cytomegalovirus (CMV) infections associated CMV viremia and CMV disease);
• Tuberculosis;
• Posterior reversible encephalopathy syndrome (PRES);
• Pure red cell aplasia (PRCA);
• Gastrointestinal perforation;
• Hyperkalemia;
• Hypertension;
• Lactose intolerance, galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption;
• Food allergies and/or presence of any dietary restrictions unless deemed by the PI/Sub-I as "Not Clinically Significant".
• Severe allergic reactions (e.g. anaphylactic reactions, angioedema).
• History of intolerance to and/or difficulty with blood sampling through venipuncture.

Where it is running

• BioPharma Services USA — St Louis, Missouri, United States

Full record on ClinicalTrials.gov

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