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

Phase 1
Completed
Conditions
Depressive Disorder
Interventions
Drug: DGX-001 Dose 2
Drug: MAD dose panel of DGX-001
Drug: DGX-001 Dose 3
Drug: DGX-001Dose 1
Drug: DGX-001 Dose 4
Registration Number
NCT05121831
Lead Sponsor
Digestome Therapeutics
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
68
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 & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Single Ascending Dose Cohort S2DGX-001 Dose 2Subjects will receive a single dose of either dose level 2 of DGX-001 or placebo
Multiple Ascending Doses Cohort M2DGX-001 Dose 2Subjects will receive multiple doses of either dose level 2 of DGX-001 or placebo
Stress Exposure Resilience Panel Cohort 1MAD dose panel of DGX-001Subjects will receive any of the MAD dose panel or placebo
Multiple Ascending Doses Cohort M3DGX-001 Dose 3Subjects will receive multiple doses of either dose level 3 of DGX-001 or placebo
Multiple Ascending Doses Cohort M1DGX-001Dose 1Subjects will receive multiple doses of either dose level 1 of DGX-001 or placebo
Single Ascending Dose Cohort S1DGX-001Dose 1Subjects will receive a single dose of either dose level 1 of DGX-001 or placebo
Single Ascending Dose Cohort S3DGX-001 Dose 3Subjects will receive a single dose of either dose level 3 of DGX-001 or placebo
Single Ascending Dose Cohort S4DGX-001 Dose 4Subjects will receive a single dose of either dose level 4 of DGX-001 or placebo
Primary Outcome Measures
NameTimeMethod
Number of treatment-emergent adverse events (TEAEs)Day1- Day14

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.

Severity of treatment-emergent adverse events as assessed by CTCAE v5.0Day 1- Day14

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.

Number of subjects with abnormal and clinically significant safety laboratory testsDay 1- Day 14

Safety laboratory tests include clinical chemistry and hematology

Number of subjects with abnormal and clinically significant electrocardiogram testDay 1- Day 21

12 lead ECGs will be collected in triplicate, which will measure heart rate, PR, QRS, QT, QTc

Number of subjects with abnormal and clinically significant urinalysis findingsDay 1-Day 21

This will include routine urine test

Secondary Outcome Measures
NameTimeMethod
Cmax in SAD and MADDay 1-day 9

Maximum plasma concentration

CL/F in SAD and MADDay 1-Day 9

Oral clearance

AUCt in SAD and MADDay 1-Day 9

Total exposure

AUC24 in SAD and MADDay 1-Day 9

Area under plasma concentration -time curve at 24 hours

tmax in SAD and MADDay 1-Day 9

Time to maximum plasma concentration

AUC∞ in SAD and MADDay 1-Day 9

Area under plasma concentration -time from time 0 to infinity

t1/2 in SAD and MADDay 1-Day 9

Terminal elimination half-life

Vz/F in SAD and MADDay 1-Day 9

Apparent volume of distribution during terminal phase after non-intravenous administration

λz in SAD and MADDay 1-Day 9

Elimination rate constant

Trial Locations

Locations (1)

CMAX Clinical Research Address

🇦🇺

Adelaide, South Australia, Australia

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