Safety and Pharmacokinetic Study of LMN-101 in Healthy Volunteers

Healthy volunteers will be sequentially assigned to the following dosing regimens:

Part A:

A single, open-label dose of 3000 mg orally (2 subjects)

Part B:

Subjects will be randomized within a dose regimen to active or placebo treatment:

• 300 mg PO TID (three times daily) given as a single 300-mg capsule of LMN-101 orally three times daily for 28 days (4 subjects) or identical-appearing placebo capsule (2 subjects).
• 1000 mg PO TID given as two 500-mg capsules of LMN-101 orally three times daily for 28 days (4 subjects) or identical-appearing placebo capsules (2 subjects).
• 3000 mg PO TID given as six 500-mg capsules of LMN-101 orally three times daily for 28 days (4 subjects) or identical-appearing placebo capsules (2 subjects).

The primary endpoint is:

• Safety and tolerability of LMN-101.

The secondary endpoints are:

• Peak serum drug concentration following administration of the initial dose and peak serum drug concentration following a course of treatment (if systemic absorption is observed).
• Area under the serum drug concentration versus time curve (AUC) following administration of the initial dose and following a course of treatment (if systemic absorption is observed).
• Induction of serum anti-drug antibodies (if systemic absorption is observed).

Inclusion criteria

• Male or female between 18 and 50 years, inclusive, at time of informed consent
• Willingness to participate after written informed consent obtained
• Available for all planned clinical visits for physical examinations, blood draws, stool collections
• General good health, without significant medical illness or abnormal physical examination findings as determined by the PI.
• Adequate bone marrow reserve, renal and liver function.

• Absolute neutrophil count ≥ 1.5 x 10e9/L
• Lymphocyte count < 6.0 x 10e9/L
• Platelet count ≥ 150 x 10e9/L
• Hemoglobin ≥ 110 g/L
• Estimated glomerular filtration rate ≥ 40 mL/min/1.73 meter squared
• Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤ 3x upper limit of normal (ULN)
• Total bilirubin ≤ 1.5x ULN
• Serum albumin ≥ 28 g/L
• Females of childbearing potential should be using and committed to continue using one of the following acceptable birth control methods:

• Sexual abstinence (inactivity) or exclusively same-sex partner for 1 month prior to screening through study completion; or
• Intrauterine device (IUD) in place for at least 1 month prior to study through study completion; or
• Stable hormonal contraception for at least 1 month prior to study through study completion; or
• Surgical sterilization (vasectomy) of male partner at least 6 months prior to study.
• To be considered of non-childbearing potential, females should be surgically sterilized (bilateral tubal ligation, hysterectomy, or bilateral oophorectomy at least 2 months prior to study) or be post-menopausal and at least 3 years since last menses.
• Male participants must use condoms during the study and through study completion.

Exclusion criteria

• Treatment with an experimental compound within 30 days.
• Treatment within 30 days or planned use within the study period with immunomodulator or immunosuppressant agent.
• Pregnancy or breastfeeding.
• Presence of any of the following clinical conditions:

• History of one or more of the following: cardiac insufficiency (NYHA III/IV), uncontrolled cardiac arrhythmias, unstable ischemic heart disease, or uncontrolled hypertension (systolic blood pressure > 170 mmHg or diastolic blood pressure > 110 mmHg).
• History of venous thromboembolic disease within 12 months, myocardial infarction, or cerebrovascular accident.
• Unstable pulmonary, renal, hepatic, endocrine or hematologic disease.
• Gastrointestinal disorder requiring ongoing care by a physician.
• Autoimmune disease, mixed connective tissue disease, scleroderma, polymyositis, or significant systemic involvement secondary to rheumatoid arthritis.
• Evidence of active malignant disease, malignancies diagnosed within the previous 5 years, or breast cancer diagnosed within the previous 5 years (except skin cancers other than melanoma).
• Known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other opportunistic infections; or major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks.
• Positive serology for human immunodeficiency virus (HIV) infection or history of other immunodeficiency illness.
• Positive serology results for hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV)
• Significant neuromuscular disease or neuropathy
• Psychiatric condition
• Alcohol or illicit drug abuse/dependency or positive urine toxicology screen for drugs of abuse other than marijuana. Alcohol and tobacco consumption are permitted.