First-in-human Study of SAN711 in Healthy Participants

Study Overview
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Brief Summary
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Phase 1, first-in-human, double-blind, randomized, placebo-controlled, parallel group, single ascending dose (SAD) and multiple ascending dose (MAD) study

Official Title
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A Phase 1 Study to Assess the Safety and Tolerability of Single and Multiple Ascending Doses of SAN711 in Healthy Participants

Conditions
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Healthy

Intervention / Treatment
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* Drug: SAN711
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy, determined by Screening medical evaluation (medical history, physical examination, vital signs, safety 12-lead electrocardiogram [ECG], and clinical laboratory evaluations, including liver and renal function tests which must be within normal limits) Body mass index (BMI) between 18.5 and 29.9 kg/m2, inclusive at Screening Non-smoker (and no other nicotine use) as determined by history (no nicotine use over the past 6 months) and by urine cotinine concentration (<500 ng/mL) at the Screening Visit and admission Female participants must be women of non-childbearing potential (WONCBP); defined as follows: surgically sterile (ie, had a hysterectomy, or bilateral oophorectomy, or bilateral salpingectomy ≥6 months prior to the first dose of study drug); or Postmenopausal (no menses) for at least 1 year prior to the first dose of study drug. Postmenopausal status must be confirmed by FSH testing at screening Exclusion Criteria: Participant has a history or evidence of any clinically significant cardiovascular, general gastrointestinal, endocrine, hematologic, hepatic, immunological, metabolic, urologic, pulmonary, neurological, dermatologic, psychiatric, renal, and/or other major disease or malignancy as judged by the investigator Participant answers yes to any of the suicide-related behaviors (actual attempt, interrupted attempt, aborted attempt, preparatory act or behavior) on the Suicidal Behavior portion of the Columbia Suicide Severity Rating Scale Participant's current alcohol intake exceeds 14 units/week for men and women (1 unit = half pint of beer, 1 glass of wine, 1 measure of spirits) Participant is unwilling to avoid use of alcohol or alcohol-containing foods, medications or beverages, within 48 hours prior to check-in Day and until final discharge Day inclusive Participant is unwilling to avoid consumption of caffeine-containing beverages within 48 hours prior to day of admission until final discharge day Participant has a history of illicit substance use OR a positive urine drug test (eg, cocaine, amphetamines, methylenedioxymethamphetamine (MDMA), barbiturates, opiates, benzodiazepines, or cannabinoids) or urine alcohol test at the Screening Visit or admission Participant has a positive test for Hepatitis B surface antigen (HBsAg), Hepatitis C, or HBsAg negative/anti-HBc positive/anti-HBs negative, or human immunodeficiency virus (HIV) 1 and/or -2 antibodies At Screening and Baseline, systolic blood pressure (SBP) greater than 140 or less than 90 mm Hg, or diastolic blood pressure (DBP) greater than 90 or less than 40 mm Hg, in the supine position, at screening or baseline. Borderline values (ie values that are within 5 mm Hg for blood pressure or 5 beats/min for heart rate) will be repeated. Subjects can be included if the repeat value is within range or still borderline, but deemed not clinically significant by the investigator Corrected QT interval using Fridericia's formula >450 msec for males and >470 msec for females Resting bradycardia (heart rate [HR] <40 beats per minute [bpm]) or tachycardia (HR >100 bpm) Personal or family history of congenital long QT syndrome or sudden death Screening or Admission ECG with QRS and/or T wave judged to be unfavorable for a consistently accurate QT measurement (eg, neuromuscular artifact that cannot be readily eliminated, arrhythmias, indistinct QRS onset, low amplitude T wave, merged T- and U-waves, prominent U waves) Evidence of atrial fibrillation, atrial flutter, complete branch block, Wolf-Parkinson-White Syndrome, or cardiac pacemaker at screening or on admission Receipt of COVID-19 vaccine within 2 weeks prior to baseline or scheduled for vaccination during the study COVID-19 infection within 90 days of screening or evidence of current COVID-19 infection within the past 4 weeks at screening, between screening and admission, or at admission If unvaccinated for COVID-19, contact with an individual with COVID-19 infection in the past 14 days at screening, between screening and admission, or at admission

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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SAN711 (SAD)<br>6 out of 8 participants per cohort (up to 7 cohorts) will be randomized to receive a single dose of SAN711 | Drug: SAN711<br>* SAN711 liquid formulation<br>|
| Placebo Comparator: Placebo (SAD)<br>2 out of 8 participants per cohort (up to 7 cohorts) will be randomized to receive a single dose of Placebo | Other: Placebo<br>* Matching placebo<br>|
| Experimental: SAN711 (MAD)<br>6 out of 8 participants per cohort (up to 3 cohorts) will be randomized to receive 14 daily doses of SAN711 | Drug: SAN711<br>* SAN711 liquid formulation<br>|
| Placebo Comparator: Placebo (MAD)<br>2 out of 8 participants per cohort (up to 3 cohorts) will be randomized to receive 14 daily doses of Placebo | Other: Placebo<br>* Matching placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment-emergent Adverse Events (TEAEs) [SAD] | Incidence of TEAEs during SAD | Initiation of dosing through 96 hours post dosing | 
| TEAEs [MAD] | Incidence of TEAEs during MAD | Initiation of dosing through 16 days post dosing | 
| Adverse Events of Special Interest (AESIs) [SAD] | Incidence of AESIs during SAD | Initiation of dosing through 96 hours post dosing | 
| AESIs [MAD] | Incidence of AESIs during MAD | Initiation of dosing through 16 days post dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK Parameters: Cmax [SAD] | Maximum observed plasma concentration at Tmax during SAD | Baseline (Predose) through 96 hours post dosing | 
| PK Parameters: Cmax [MAD] | Maximum observed plasma concentration at Tmax during MAD | Day 1 (Predose) through Day 16 | 
| PK Parameters: Tmax [SAD] | Time of maximum observed plasma concentration during SAD | Baseline (Predose) through 96 hours post dosing | 
| PK Parameters: Tmax [MAD] | Time of maximum observed plasma concentration during MAD | Day 1 (Predose) through Day 16 | 
| PK Parameters: t1/2 [SAD] | Apparent terminal phase half-life during SAD | Baseline (Predose) through 96 hours post dosing | 
| PK Parameters: t1/2 [MAD] | Apparent terminal phase half-life during MAD | Day 1 (Predose) through Day 16 | 
| PK Parameters: AUC-last [SAD] | Area under the plasma concentration time curve from time zero to T-last, the time at which Last measurable plasma concentration (C-last) is observed during SAD | Baseline (Predose) through 96 hours post dosing | 
| PK Parameters: AUC-last [MAD] | Area under the plasma concentration time curve from time zero to T-last, the time at which Last measurable plasma concentration (C-last) is observed during MAD | Day 1 (Predose) through Day 16 | 
| PK Parameters: AUC-inf [SAD] | Area under the plasma concentration time curve extrapolated to infinity during SAD | Baseline (Predose) through 96 hours post dosing | 
| PK Parameters: AUC-inf [MAD] | Area under the plasma concentration time curve extrapolated to infinity during MAD | Day 1 (Predose) through Day 16 |