Clinical trial NCT04532957: A Multiple Ascending Dose Study to Investigate Safety of KBP-7072 in Healthy Subjects
Official title: A Phase I, Double Blind, Placebo Controlled, Multiple Oral Dose, Safety, Tolerability, and Pharmacokinetic Study of KBP-7072 in Healthy Male and Female Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: KBP-7072
Multiple ascending dose
Healthy Subjects
Antibiotics
Tetracycline
Lead sponsor: KBP Biosciences
Sponsor class: INDUSTRY
Collaborators: name: Covance
First posted: 2020-08-31
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a double-blind, placebo-controlled, multiple oral dose study to evaluate safety, tolerability, and pharmacokinetic of KBP-7072 in healthy subjects.

Detailed description: This was a double-blind, randomized, placebo-controlled, parallel-group, multiple oral dose study. Overall, a total of 24 subjects were studied in 3 groups (Groups 1 to 3); with each group consisting of 8 subjects (6 subjects receiving KBP-7072 and 2 subjects receiving placebo). Groups 1 and 2 evaluated 100 and 200 mg QD, respectively. The dose level of 150 mg QD evaluated in Group 3 was determined based on data obtained from Group 2 of this stud

Eligibility criteria: Inclusion Criteria:

1. Females of nonchildbearing potential or males, of any race, between 18 and 50 years of age, inclusive, at screening.
2. Body mass index between 18.0 and 30.0 kg/m2, inclusive, at screening.
3. In good health, determined by no clinically significant findings from medical history, physical and ophthalmologic examinations, 12 lead ECG, vital sign measurements, and clinical laboratory evaluations (congenital nonhemolytic hyperbilirubinemia \[eg, suspicion of Gilbert's syndrome based on total and direct bilirubin\] is not acceptable) at screening and check in as assessed by the investigator (or designee).
4. Females of nonchildbearing potential defined as permanently sterile or postmenopausal. Males will agree to use contraception.
5. Able to comprehend and willing to sign an ICF and to abide by the study restrictions.

Exclusion Criteria:

1. Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the investigator (or designee).
2. History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the investigator (or designee).
3. History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy and hernia repair will be allowed). Cholecystectomy will not be allowed.
4. Alanine aminotransferase or AST ≥ 1 × ULN. Assessments may be repeated once if outside the range at screening and/or check-in, at the discretion of the investigator.
5. Fibroscan controlled attenuation parameter (CAP) \> 238 dB/m and vibration controlled transient elastography (VCTE) \> 7 kPa.

Primary outcomes:
measure: Safety of KBP-7072 by assessing the number and severity of adverse events, laboratory abnormalities, ECGs, vital signs, and physical examinations.
timeFrame: Day 1 - 10
Secondary outcomes:
measure: Pharmacokinetics Parameters: Area under the plasma concentration-time curve (AUC) from time zero to time of last quantifiable concentration (AUC0-tlast),
timeFrame: Day 1 predose and at 0.5, 1, 2, 4, 6, 10, 12, 18, and 24 hours postdose; on Days 4, 7, 8 and 9 predose and on Day 10 predose and at 0.5, 1, 2, 4, 6, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours postdose.
measure: Pharmacokinetics Parameters: AUC over a dosing interval (AUC0-τ), from time zero to time of last quantifiable concentration (AUC0-tlast)
timeFrame: Day 1 predose and at 0.5, 1, 2, 4, 6, 10, 12, 18, and 24 hours postdose; on Days 4, 7, 8 and 9 predose and on Day 10 predose and at 0.5, 1, 2, 4, 6, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours postdose.
measure: Pharmacokinetics Parameters: Maximum observed plasma concentration (Cmax)
timeFrame: Day 1 predose and at 0.5, 1, 2, 4, 6, 10, 12, 18, and 24 hours postdose; on Days 4, 7, 8 and 9 predose and on Day 10 predose and at 0.5, 1, 2, 4, 6, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours postdose.
measure: Pharmacokinetics Parameters: time of the maximum observed plasma concentration (Tmax)
timeFrame: Day 1 predose and at 0.5, 1, 2, 4, 6, 10, 12, 18, and 24 hours postdose; on Days 4, 7, 8 and 9 predose and on Day 10 predose and at 0.5, 1, 2, 4, 6, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours postdose.
measure: Pharmacokinetics Parameters: apparent terminal elimination half-life (t1/2)
timeFrame: Day 1 predose and at 0.5, 1, 2, 4, 6, 10, 12, 18, and 24 hours postdose; on Days 4, 7, 8 and 9 predose and on Day 10 predose and at 0.5, 1, 2, 4, 6, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours postdose.
measure: Pharmacokinetics Parameters: observed accumulation ratio based on AUC0-τ (ARAUC0-τ)
timeFrame: Day 1 predose and at 0.5, 1, 2, 4, 6, 10, 12, 18, and 24 hours postdose; on Days 4, 7, 8 and 9 predose and on Day 10 predose and at 0.5, 1, 2, 4, 6, 10, 12, 18, 24, 48, 72, 96, 120, 144, and 168 hours postdose.
measure: Pharmacokinetics Parameters: amount of drug excreted in urine (Ae)
timeFrame: Day 1 at predose (spot collection), 0-6, 6-12, and 12-24 hours postdose, on Days 4, 7, 8 and 9 at predose (spot collection) and on Day 10 at 0-6, 6-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144, and 144-168 hours postdose.
Other outcomes:
Locations:
city: Daytona Beach
country: United States
facility: Covance Clinical Research Unit
state: Florida
Study officials:
affiliation: KBP Biosciences
name: James McCabe, MD
role: STUDY_DIRECTOR
References: