A First in Human Study to Assess the Safety, Tolerability, and Pharmacokinetics of DGX-001

Study Overview
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Brief Summary
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This is a phase 1, randomized, double-blind, placebo-controlled, SAD and MAD study in healthy adult volunteers. DGX-001 is a peptide being investigated for the treatment of the major depressive disorder. This study will examine the safety and tolerability of increasing doses of DGX-001 and, in an exploratory way, potential moderators and functional markers of its activity.

Detailed Description
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The study will be conducted in three parts, Part 1 consisting of SAD cohorts and Part 2 consisting of MAD cohorts and Part 3 consisting of one cohorts of stress exposure resilience panel. In Part 1, approximately 32 adult healthy volunteers will be enrolled sequentially into 1 of 4 single-dose cohorts and will be randomized to receive either a dose of DGX-001 or a placebo. In Part 2, approximately 24 adult healthy volunteers will be enrolled into 1 of 3 multiple-dose cohorts. An adaptive dose-escalation schedule will be employed for both the SAD and MAD parts of the study. In Part 3, 14 subjects will be enrolled in 1 cohorts to further explore the pharmacodynamic effect of DGX-001 under a physiological challenge.

Official Title
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A Phase 1, Randomized, Double-blind, Placebo-controlled, Safety, Tolerability and Pharmacokinetic Study of Escalating Single and Multiple Doses of DGX-001 in Healthy Volunteers Followed by a Stress Exposure Resilience Panel

Conditions
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Depressive Disorder

Intervention / Treatment
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* Drug: DGX-001Dose 1
* Drug: DGX-001 Dose 2
* Drug: DGX-001 Dose 3
* Drug: DGX-001 Dose 4
* Drug: MAD dose panel of DGX-001


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female healthy adult volunteers between 18 to 65 years of age (Both inclusive). The subject's BMI is between 18 and 32 kg/m2. Female subjects with childbearing potential must have a negative serum pregnancy test. The subject is medically healthy with no clinically significant or relevant abnormalities in medical history, physical exam, vital signs, electrocardiogram (ECG), and laboratory evaluations (hematology, chemistry, and urinalysis) as assessed by the Investigator. Exclusion Criteria: The subject has a current or recurrent disease that could affect the action, absorption or disposition of the investigational medicinal product or could affect clinical or laboratory assessments. The subject has abnormal renal function test ( <60mL/min, i.e., GFR by Cockroft/Gault) at screening or baseline. The subject has evidence of Gilbert's Syndrome or abnormal liver function test (LFTs >1.5x ULN) at screening or baseline. The subject has had a cholecystectomy or a history of cholecystitis. The subject has clinically significant 12-lead ECG abnormalities, including QTc of 450ms for males and 470ms for females (average of triplicate measures) for any pre-randomization ECG assessment. The subject has a current or relevant history of physical or psychiatric illness. The subject has a documented history of HIV antibody or tested positive for hepatitis B surface antigen (HBsAg) or Hepatitis C virus (HCV) antibody at screening. The subject received an investigational agent within the last 30 days prior to Screening or five half-lives (if known) prior to Screening. The subject has a history of alcohol or other substance abuse within the 12 months prior to dosing. The subject is currently using any medication (including over-the-counter [OTC], herbal or homeopathic preparations), except for hormonal replacement therapy or hormonal contraceptives, that in the opinion of the investigator can not be discontinued and avoided for four weeks before the first dose throughout the study period.

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: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Part 1 and Part 2 of the study will have a parallel assignment and Part 3 of the study will have a parallel assignment with a crossover design.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Ascending Dose Cohort S1<br>Subjects will receive a single dose of either dose level 1 of DGX-001 or placebo | Drug: DGX-001Dose 1<br>* Dose level 1 of DGX-001<br>* Other names: DGX-001;|
| Experimental: Single Ascending Dose Cohort S2<br>Subjects will receive a single dose of either dose level 2 of DGX-001 or placebo | Drug: DGX-001 Dose 2<br>* Dose level 2 of DGX-001<br>* Other names: DGX-001;|
| Experimental: Single Ascending Dose Cohort S3<br>Subjects will receive a single dose of either dose level 3 of DGX-001 or placebo | Drug: DGX-001 Dose 3<br>* Dose level 3 of DGX-001<br>* Other names: DGX-001;|
| Experimental: Single Ascending Dose Cohort S4<br>Subjects will receive a single dose of either dose level 4 of DGX-001 or placebo | Drug: DGX-001 Dose 4<br>* Dose level 4 of DGX-001<br>* Other names: DGX-001;|
| Experimental: Multiple Ascending Doses Cohort M1<br>Subjects will receive multiple doses of either dose level 1 of DGX-001 or placebo | Drug: DGX-001Dose 1<br>* Dose level 1 of DGX-001<br>* Other names: DGX-001;|
| Experimental: Multiple Ascending Doses Cohort M2<br>Subjects will receive multiple doses of either dose level 2 of DGX-001 or placebo | Drug: DGX-001 Dose 2<br>* Dose level 2 of DGX-001<br>* Other names: DGX-001;|
| Experimental: Multiple Ascending Doses Cohort M3<br>Subjects will receive multiple doses of either dose level 3 of DGX-001 or placebo | Drug: DGX-001 Dose 3<br>* Dose level 3 of DGX-001<br>* Other names: DGX-001;|
| Experimental: Stress Exposure Resilience Panel Cohort 1<br>Subjects will receive any of the MAD dose panel or placebo | Drug: MAD dose panel of DGX-001<br>* Dose levels confirmed through SAD and MAD<br>* Other names: DGX-001;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of treatment-emergent adverse events (TEAEs) | A TEAE is any event that is not present before the initiation of the investigational product or any event already present that worsens in either intensity or frequency following exposure to the investigational product. | Day1- Day14 | 
| Severity of treatment-emergent adverse events as assessed by CTCAE v5.0 | A TEAE is any event that is not present before the initiation of the investigational product or any event already present that worsens in either intensity or frequency following exposure to the investigational product. | Day 1- Day14 | 
| Number of subjects with abnormal and clinically significant safety laboratory tests | Safety laboratory tests include clinical chemistry and hematology | Day 1- Day 14 | 
| Number of subjects with abnormal and clinically significant electrocardiogram test | 12 lead ECGs will be collected in triplicate, which will measure heart rate, PR, QRS, QT, QTc | Day 1- Day 21 | 
| Number of subjects with abnormal and clinically significant urinalysis findings | This will include routine urine test | Day 1-Day 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUCt in SAD and MAD | Total exposure | Day 1-Day 9 | 
| AUC24 in SAD and MAD | Area under plasma concentration -time curve at 24 hours | Day 1-Day 9 | 
| AUC∞ in SAD and MAD | Area under plasma concentration -time from time 0 to infinity | Day 1-Day 9 | 
| Cmax in SAD and MAD | Maximum plasma concentration | Day 1-day 9 | 
| tmax in SAD and MAD | Time to maximum plasma concentration | Day 1-Day 9 | 
| t1/2 in SAD and MAD | Terminal elimination half-life | Day 1-Day 9 | 
| CL/F in SAD and MAD | Oral clearance | Day 1-Day 9 | 
| Vz/F in SAD and MAD | Apparent volume of distribution during terminal phase after non-intravenous administration | Day 1-Day 9 | 
| λz in SAD and MAD | Elimination rate constant | Day 1-Day 9 |