Safety and Tolerability Study of LBS-008 in Healthy Adult Subjects After Single and Multiple Doses

Study Overview
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Brief Summary
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This is a single center, randomized, double-blind, placebo-controlled, Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) study is planned to assess safety, pharmacokinetics (PK), and pharmacodynamics of LBS-008 in healthy adult volunteers.

Official Title
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A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LBS-008 in Healthy Adult Subjects

Conditions
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Healthy Volunteer

Intervention / Treatment
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* Drug: LBS-008
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject is male or female, 18 to 65 years of age, inclusive, at screening. The subject voluntarily consents to participate in this study and provides written informed consent before the start of any study-specific procedures. The subject is willing and able to remain in the study unit for the entire duration of the confinement period and return for outpatient visits. Female subjects must be of nonchildbearing potential (defined as surgically sterile [i.e., had a bilateral tubal ligation, hysterectomy, or bilateral oophorectomy at least 6 months before the dose of study drug] or postmenopausal for at least 1 year before study drug administration confirmed by FSH test at screening; FSH level >40 mIU/mL). Female subjects may also be considered of non-childbearing if they have a confirmed medical condition which would deem the subject as infertile. E.g. MRKH Syndrome (Mullerian Agenesis) or another applicable condition. Male subjects must be surgically sterile (i.e., vasectomy) for at least 3 months before screening; or remain abstinent or agree to use a highly effective form of contraception when sexually active with a female partner for 90 days after study drug administration. Highly effective contraception requires use of a condom and appropriate contraceptive measures for your female partner (i.e. oral, injected or implanted hormonal methods, or placement of an intrauterine device or intrauterine system). This requirement does not apply to subjects in a same sex relationship and female partners of non-childbearing potential. The subject has a body mass index (BMI) of 18 to 30 kg/m2, inclusive, and weighs 50 to 100 kg (110 to 220 pounds), inclusive, at screening and check-in. The subject is considered to be in stable health by the investigator. The subject agrees to comply with all protocol requirements. Exclusion Criteria: Any significant acute or chronic medical illness including history or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, oncologic, or psychiatric disease Vitamin A deficiency. Any recent viral or bacterial infection. Participated in any clinical study in last 6 weeks. History of significant drug allergy History of significant vision, ocular or retinal disorder. Recent surgery, blood transfusion, drug or alcohol abuse and use of tobacco or nicotine containing products in past month. Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECGs, or clinical laboratory determinations Other protocol-defined inclusion/exclusion criteria could apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Basic Science
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SAD - Cohort 1<br>50 mg LBS-008 or placebo | Drug: LBS-008<br>* LBS-008 oral capsules<br>Drug: Placebos<br>* Oral capsules<br>|
| Experimental: SAD - Cohort 2<br>100 mg LBS-008 or placebo | Drug: LBS-008<br>* LBS-008 oral capsules<br>Drug: Placebos<br>* Oral capsules<br>|
| Experimental: SAD - Cohort 3<br>200 mg LBS-008 or placebo | Drug: LBS-008<br>* LBS-008 oral capsules<br>Drug: Placebos<br>* Oral capsules<br>|
| Experimental: SAD - Cohort 4<br>400 mg LBS-008 or placebo | Drug: LBS-008<br>* LBS-008 oral capsules<br>Drug: Placebos<br>* Oral capsules<br>|
| Experimental: SAD - Cohort 5<br>25 mg LBS-008 or placebo | Drug: LBS-008<br>* LBS-008 oral capsules<br>Drug: Placebos<br>* Oral capsules<br>|
| Experimental: MAD - Cohort 1<br>10 mg LBS-008 or placebo | Drug: LBS-008<br>* LBS-008 oral capsules<br>Drug: Placebos<br>* Oral capsules<br>|
| Experimental: MAD - Cohort 2<br>25 mg LBS-008 or placebo | Drug: LBS-008<br>* LBS-008 oral capsules<br>Drug: Placebos<br>* Oral capsules<br>|
| Experimental: MAD - Cohort 3<br>5 mg LBS-008 or placebo | Drug: LBS-008<br>* LBS-008 oral capsules<br>Drug: Placebos<br>* Oral capsules<br>|
| Experimental: MAD - Cohort 4<br>12 mg LBS-008 or placebo | Drug: LBS-008<br>* LBS-008 oral capsules<br>Drug: Placebos<br>* Oral capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration versus time curve from time 0 to the last timepoint with quantifiable concentration (AUC0-t) |  | SAD portion: Day 1 to Day 8; MAD portion: Day 1 to Day 28 | 
| Area under the plasma concentration versus time curve from time 0 extrapolated to infinity (AUC0-inf) |  | SAD portion: Day 1 to Day 8; MAD portion: Day 1 to Day 28 | 
| Maximum observed plasma concentration (Cmax) |  | SAD portion: Day 1 to Day 6; MAD portion: Day 1 to Day 28 | 
| Time to maximum observed plasma concentration (Tmax) |  | SAD portion: Day 1 to Day 8; MAD portion: Day 1 to Day 28 | 
| Terminal elimination rate constant |  | SAD portion: Day 1 to Day 8; MAD portion: Day 1 to Day 28 | 
| Terminal phase half-life (t1/2) |  | SAD portion: Day 1 to Day 8; MAD portion: Day 1 to Day 28 | 
| Apparent total body clearance (CL/F) |  | SAD portion: Day 1 to Day 8; MAD portion: Day 1 to Day 28 | 
| Apparent volume of distribution (Vz/F) |  | SAD portion: Day 1 to Day 8; MAD portion: Day 1 to Day 28 | 
| Number of participants with Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs leading to discontinuation. |  | SAD portion: Day 1 to Day 8; MAD portion: Day 1 to Day 28 |