Depressive Disorder
Conditions
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.
Interventions
DRUGMAD dose panel of DGX-001
Dose levels confirmed through SAD and MAD
DRUGDGX-001Dose 1
Dose level 1 of DGX-001
DRUGDGX-001 Dose 2
Dose level 2 of DGX-001
DRUGDGX-001 Dose 3
Dose level 3 of DGX-001
DRUGDGX-001 Dose 4
Dose level 4 of DGX-001
Sponsors
Digestome Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Double-blind
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 v5.0 | Day 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 tests | Day 1- Day 14 | Safety laboratory tests include clinical chemistry and hematology |
| Number of subjects with abnormal and clinically significant electrocardiogram test | Day 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 findings | Day 1-Day 21 | This will include routine urine test |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| t1/2 in SAD and MAD | Day 1-Day 9 | Terminal elimination half-life |
| CL/F in SAD and MAD | Day 1-Day 9 | Oral clearance |
| AUCt in SAD and MAD | Day 1-Day 9 | Total exposure |
| λz in SAD and MAD | Day 1-Day 9 | Elimination rate constant |
| Vz/F in SAD and MAD | Day 1-Day 9 | Apparent volume of distribution during terminal phase after non-intravenous administration |
| AUC24 in SAD and MAD | Day 1-Day 9 | Area under plasma concentration -time curve at 24 hours |
| AUC∞ in SAD and MAD | Day 1-Day 9 | Area under plasma concentration -time from time 0 to infinity |
| Cmax in SAD and MAD | Day 1-day 9 | Maximum plasma concentration |
| tmax in SAD and MAD | Day 1-Day 9 | Time to maximum plasma concentration |
Countries
Australia
Outcome results
None listed