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

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

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.

Study Overview

• Status: Completed
• Conditions: Depressive Disorder
• Intervention / Treatment: 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

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • CMAX Clinical Research Address

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Male or female healthy adult volunteers between 18 to 65 years of age (Both inclusive).
2. The subject's BMI is between 18 and 32 kg/m2.
3. Female subjects with childbearing potential must have a negative serum pregnancy test.
4. 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:

1. 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.
2. The subject has abnormal renal function test ( <60mL/min, i.e., GFR by Cockroft/Gault) at screening or baseline.
3. The subject has evidence of Gilbert's Syndrome or abnormal liver function test (LFTs >1.5x ULN) at screening or baseline.
4. The subject has had a cholecystectomy or a history of cholecystitis.
5. 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.
6. The subject has a current or relevant history of physical or psychiatric illness.
7. 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.
8. The subject received an investigational agent within the last 30 days prior to Screening or five half-lives (if known) prior to Screening.
9. The subject has a history of alcohol or other substance abuse within the 12 months prior to dosing.
10. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

8

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Digestome Therapeutics
• Investigators: Study Director: Igor Grachev, Digestome Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2022
• Primary Completion (Actual): November 6, 2022
• Study Completion (Actual): November 6, 2022

Study Registration Dates

• First Submitted: November 5, 2021
• First Submitted That Met QC Criteria: November 5, 2021
• First Posted (Actual): November 16, 2021

Study Record Updates

• Last Update Posted (Actual): June 22, 2023
• Last Update Submitted That Met QC Criteria: June 19, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder
• Other Study ID Numbers: DGX-001-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No