Safety
Conditions
Brief summary
This is the first in human study of MOR107. It is a 2 part, single centre, double-blind, randomised, placebo-controlled study in healthy male subjects. Part 1 is a single ascending dose study, and Part 2 is a parallel group, dose range finding study in healthy male subjects on a low sodium diet.
Detailed description
MOR107 is an angiotensin 2 receptor (AT2R) agonist with the potential to treat a wide range of diseases through activation of the protective arm of the renin-angiotensin system. In this study MOR107 will be administered to humans for the first time. The study will enroll healthy male subjects and is split into two sequential parts, both of which have a single centre, double-blind, randomised, placebo-controlled design. Part 1 will evaluate the safety, tolerability and pharmacokinetics (PK) of single ascending doses of MOR107. Part 2 will evaluate the pharmacodynamics, safety, tolerability and PK of three different doses of MOR107 in healthy male subjects who will be fed a low sodium diet in order to increase AT2R expression.
Interventions
DRUGPlacebo
Solution for injection manufactured to match MOR107 solution for injection
DRUGMOR107
MOR107 solution for injection
OTHERLow sodium diet
Diet designed to restrict sodium intake to 40 mmol/day
Sponsors
Quotient Clinical
Alan Richardson
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Part 1: single ascending doses Part 2: parallel group
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria: 1. Healthy males 2. Age 18 to 45 years of age 3. Body mass index of 18.0 to 32.0 kg/m2 4. For Part 2, subjects must have at least a 25% reduction in 24 hour urinary sodium excretion on Day -2 compared with admission Key
Exclusion criteria
1. Subjects who have received any IMP in a clinical research study within the previous three months 2. Regular alcohol consumption \>21 units per week (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine) 3. Current smokers and those who have smoked within the last 12 months. A breath carbon monoxide reading of greater than 10 ppm at screening/admission 4. Current smokers of e-cigarettes and nicotine replacement products and those who have smoked these products within the last 12 months 5. Clinically significant abnormal biochemistry, haematology or urinalysis as judged by the investigator 6. Positive drugs of abuse test result 7. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results 8. History of psychiatric disorder, cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal disease as judged by the investigator 9. Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of treatment-emergent adverse events (safety and tolerability) | Up to 10 days post-dose | Reporting of adverse events, physical examination, injection site assessment, vital signs, ECG, and clinical chemistry, haematology and urinalysis |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum observed MOR107 concentration (Cmax) | Up to 48 hours post-dose | Plasma PK parameter |
| Concentration of MOR107 at 12 hours post-dose (C12) | 12 hours post-dose | Plasma PK parameter |
| Concentration of MOR107 at 24 hours post-dose (C24) | 24 hours post-dose | Plasma PK parameter |
| Area under the curve from 0 time to last measurable MOR107 concentration (AUC0-t) | Up to 48 hours post-dose | Plasma PK parameter |
| Area under the curve from 0 time to infinity for MOR107 (AUC0-inf) | Up to 48 hours post-dose | Plasma PK parameter |
| Percentage of AUC(0-inf) for MOR107 extrapolated beyond last measured time point (AUC%extrap) | Up to 48 hours post-dose | Plasma PK parameter |
| Slope of the apparent elimination phase for MOR107 (Lambda-z) | Up to 48 hours post-dose | Plasma PK parameter |
| Apparent elimination half-life for MOR107 (T-half) | Up 48 hours post-dose | Plasma PK parameter |
| Time from dosing at which the maximum MOR107 concentration was observed (Tmax) | Up to 48 hours post-dose | Plasma PK parameter |
| MOR107 AUC(0-t) normalised for dose (AUC[0-t]/D) | Up to 48 hours post-dose | Plasma PK parameter |
| MOR107 AUC(0-inf) normalised for dose (AUC[0-inf]/D) | Up to 48 hours post-dose | Plasma PK parameter |
| Amount of MOR107 excreted in the urine over a specified period of time after dosing (Ae) | Up to 48 hours post-dose | Urine PK parameter |
| Cumulative amount of MOR107 excreted in the urine (CumAe) | Up to 48 hours post-dose | Urine PK parameter |
| Amount of MOR107 excreted in the urine over a specified period of time after dosing, expressed as a percentage of the administered dose (Ae%) | Up to 48 hours post-dose | Urine PK parameter |
| Cumulative amount of MOR107 excreted in the urine, expressed as a percentage of the administered dose (CumAe%) | Up to 48 hours post-dose | Urine PK parameter |
| Renal clearance: the apparent volume of plasma cleared per unit time via renal elimination (CLr) | Up to 48 hours post-dose | Urine PK parameter |
| MOR107 Cmax normalised for dose (Cmax/D) | Up to 48 hours post-dose | Plasma PK parameter |
Countries
United Kingdom
Outcome results
None listed