An Open-Label, Partial Crossover, Single-Dose Study to Evaluate the Pharmacokinetics, Dose-Proportionality, and Safety/Tolerability of Tablet Versus Capsule Formulations of KBP 5074 in Healthy Subjects
Overview
- Phase
- Phase 1
- Intervention
- KBP-5074 Capsule
- Conditions
- Bioequivalence
- Sponsor
- KBP Biosciences
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- AUClast
- Status
- Completed
- Last Updated
- 4 months ago
Overview
Brief Summary
This is an open-label, partial crossover, single-dose study to evaluate the pharmacokinetics (PK), dose proportionality, and safety/tolerability of tablet versus capsule formulations of KBP-5074 in healthy subjects. The study is designed to evaluate the PK of a new tablet formulation versus that of the current capsule formulation. Data derived from this study, in addition to preclinical data and chemistry, manufacturing, and controls, will provide a basis for dose selection in future studies.
Detailed Description
Twenty healthy subjects will be allocated 4:1 to either the crossover study groups (16 subjects) or to the 0.25 mg tablet single dose treatment (4 subjects). Subjects allocated to the crossover study groups will be randomized 1:1 to 0.5 mg tablet/capsule (8 subjects) or 1.0 mg tablet/capsule (8 subjects). Within the crossover study groups, subjects will be further randomized to receive a single dose of KBP-5074 (0.5 mg or 1.0 mg) in either capsule or tablet formulation in a 2-period crossover design with a 2-week washout period. The study duration for subjects in the crossover study groups will be approximately 7 weeks, which includes a 3-week screening period, and the 2 crossover single dose periods, which will be followed by a 2-week washout/follow-up period, respectively. Subjects allocated to the 0.25 mg dose cohort (n=4) will receive a single dose of 0.25 mg in tablet formulation only. The 0.25 mg tablet cohort will provide additional data for the evaluation of dose exposure for the tablet formulation. The study duration for the single dose arm will be 5 weeks, which includes a 3-week screening period, and the single dose which will be followed by a 2 week washout period.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Physically and mentally healthy male and females, aged 18 to 45, inclusive;
- •Body mass index (BMI) between 18 to 30 kg/m2, inclusive;
- •Nicotine-free (cigarettes, pipe, cigar, chewing tobacco, nicotine patches, etc.) for at least 6 months prior to Screening until the end of the study;
- •Normal renal function as defined by estimated glomerular filtration rate \>90 mL/min/1.73m2;
- •Willing to remain in the study facility for the duration of the domicile period and able to return for all out-patient visits;
- •Ability to understand and sign written informed consent, which must be obtained prior to any study-related procedures being completed;
- •Willing to avoid adding salt substitutes that contain potassium chloride or potassium lactate to food from 7 days prior to dosing through the duration of the study;
- •Women of childbearing potential (WOCBP), must agree to 2 medically accepted, effective methods of birth control during the study and for 90 days after the end of the study. Adequate methods of contraception are defined as those that result in a low failure rate (\<1% per year) when used consistently and correctly. Such methods include the use of oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products (such as an intrauterine diaphragm, condoms, or spermicides);
- •Women of childbearing potential are defined as women who are not surgically or chemically sterilized, including hysterectomy or bilateral oophorectomy (tubal ligation is not acceptable), and who are between menarche and 1 year post-menopause; and
- •Post-menopausal is defined as amenorrhoeic for at least 1 year prior to screening AND, if aged under 45 years have a serum follicle stimulating hormone (FSH) level of at least 30 IU/L. Women who are taking hormone replacement therapy (HRT) do not have to have FSH assessments, but the amenorrhea (before starting HRT) must have been naturally (spontaneously) occurring and have been accompanied by an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms);
Exclusion Criteria
- •History of any illness, that, in the opinion of the Investigator, could confound the results of the study or pose an additional risk to the subject by their participation in the study ;
- •History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease;
- •Any surgical or medical condition that could interfere with the absorption, distribution, metabolism, or excretion of the IMP;
- •History of any clinically significant drug allergy as per the Investigator's judgment;
- •History of alcohol abuse or illicit drug use within 2 years of Screening;
- •Use of marijuana (including prescribed marijuana) within 3 months prior to Screening;
- •Use of nicotine within 6 months prior to screening;
- •Use of any prescription or over-the-counter medication, vitamins/herbal supplements (with the exception of hormonal contraceptives or HRT and sporadic use of acetaminophen or ibuprofen) within 7 days (14 days if the drug is a potential enzyme inducer) prior to study allocation;
- •Has taken any investigational medicinal product (IMP) within 30 days or 5 half-lives of that IMP (whichever is longer) prior to dosing;
- •Donation of blood or blood products within 30 days of dosing;
Arms & Interventions
KBP-5074 Capsule
KBP-5074 capsule, 0.5 mg or 1.0 mg, QD, single dose
Intervention: KBP-5074 Capsule
KBP-5074 Tablet
KBP-5074 tablet, 0.5 mg or 1.0 mg, QD, single dose
Intervention: KBP-5074 Tablet
Outcomes
Primary Outcomes
AUClast
Time Frame: Through 312 hours
Area under the plasma concentration-time curve (AUC) from time 0 to the time of the last quantifiable plasma concentration