A Multiple Ascending Dose Study to Investigate Safety of KBP-7072 in Healthy Subjects

Study Overview
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Brief Summary
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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
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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

Official Title
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A Phase I, Double Blind, Placebo Controlled, Multiple Oral Dose, Safety, Tolerability, and Pharmacokinetic Study of KBP-7072 in Healthy Male and Female Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: KBP-7072
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females of nonchildbearing potential or males, of any race, between 18 and 50 years of age, inclusive, at screening. Body mass index between 18.0 and 30.0 kg/m2, inclusive, at screening. 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). Females of nonchildbearing potential defined as permanently sterile or postmenopausal. Males will agree to use contraception. Able to comprehend and willing to sign an ICF and to abide by the study restrictions. Exclusion Criteria: 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). History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the investigator (or designee). 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. 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. Fibroscan controlled attenuation parameter (CAP) > 238 dB/m and vibration controlled transient elastography (VCTE) > 7 kPa.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>Multiple doses 100mg Healthy subjects receive multiple doses of KBP-7072 (100mg) or Placebo (100mg) QD capsules daily for a total of 10 days | Drug: KBP-7072<br>* QD oral capsules<br>Drug: Placebo<br>* matching placebo capsules<br>|
| Experimental: Group 2<br>Multiple doses 200mg Healthy subjects receive multiple doses of KBP-7072 (200mg) or Placebo (200mg) QD capsules daily for a total of 10 days | Drug: KBP-7072<br>* QD oral capsules<br>Drug: Placebo<br>* matching placebo capsules<br>|
| Experimental: Group 3<br>Multiple doses dose tbd Healthy subjects receive multiple doses of KBP-7072 (tbd) or Placebo(tbd) QD capsules daily for a total of 10 days | Drug: KBP-7072<br>* QD oral capsules<br>Drug: Placebo<br>* matching placebo capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of KBP-7072 by assessing the number and severity of adverse events, laboratory abnormalities, ECGs, vital signs, and physical examinations. | Safety Assessment evaluated through adverse events, laboratory evaluations, vital signs, ECGs, and physical examinations | Day 1 - 10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics Parameters: Area under the plasma concentration-time curve (AUC) from time zero to time of last quantifiable concentration (AUC0-tlast), | Area under the plasma concentration-time curve (AUC) from time zero to time of last quantifiable concentration (AUC0-tlast) - Plasma | 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. | 
| Pharmacokinetics Parameters: AUC over a dosing interval (AUC0-τ), from time zero to time of last quantifiable concentration (AUC0-tlast) | AUC over a dosing interval (AUC0-τ) - Plamsa | 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. | 
| Pharmacokinetics Parameters: Maximum observed plasma concentration (Cmax) | Maximum observed plasma concentration (Cmax) - Plasma | 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. | 
| Pharmacokinetics Parameters: time of the maximum observed plasma concentration (Tmax) | Time of the maximum observed plasma concentration (Tmax) - Plasma | 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. | 
| Pharmacokinetics Parameters: apparent terminal elimination half-life (t1/2) | Apparent terminal elimination half-life (t1/2) - Plasma | 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. | 
| Pharmacokinetics Parameters: observed accumulation ratio based on AUC0-τ (ARAUC0-τ) | Observed accumulation ratio based on AUC0-τ (ARAUC0-τ) - Plasma | 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. | 
| Pharmacokinetics Parameters: amount of drug excreted in urine (Ae) | Amount of drug excreted in urine (Ae) - Urine | 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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KBP-7072, Multiple ascending dose, Healthy Subjects, Antibiotics, Tetracycline