Clinical trial NCT03067363: First in Human Single Ascending Dose Study of MOR107
Official title: Assessment of Safety, Tolerability and Pharmacokinetics of Single Ascending Subcutaneous Doses of MOR107 in Healthy Male Subjects and Pharmacodynamics in Healthy Male Subjects on a Low Sodium Diet
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Safety
Lead sponsor: LanthioPep BV
Sponsor class: INDUSTRY
Collaborators: name: Quotient Clinical
First posted: 2017-03-01
Enrollment: 24
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Part 1: single ascending doses Part 2: parallel group
Primary purpose: BASIC_SCIENCE

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.

Eligibility 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

Primary outcomes:
measure: Incidence of treatment-emergent adverse events (safety and tolerability)
timeFrame: Up to 10 days post-dose
Secondary outcomes:
measure: Time from dosing at which the maximum MOR107 concentration was observed (Tmax)
timeFrame: Up to 48 hours post-dose
measure: Maximum observed MOR107 concentration (Cmax)
timeFrame: Up to 48 hours post-dose
measure: Concentration of MOR107 at 12 hours post-dose (C12)
timeFrame: 12 hours post-dose
measure: Concentration of MOR107 at 24 hours post-dose (C24)
timeFrame: 24 hours post-dose
measure: Area under the curve from 0 time to last measurable MOR107 concentration (AUC0-t)
timeFrame: Up to 48 hours post-dose
measure: Area under the curve from 0 time to infinity for MOR107 (AUC0-inf)
timeFrame: Up to 48 hours post-dose
measure: Percentage of AUC(0-inf) for MOR107 extrapolated beyond last measured time point (AUC%extrap)
timeFrame: Up to 48 hours post-dose
measure: Slope of the apparent elimination phase for MOR107 (Lambda-z)
timeFrame: Up to 48 hours post-dose
measure: Apparent elimination half-life for MOR107 (T-half)
timeFrame: Up 48 hours post-dose
measure: MOR107 Cmax normalised for dose (Cmax/D)
timeFrame: Up to 48 hours post-dose
measure: MOR107 AUC(0-t) normalised for dose (AUC[0-t]/D)
timeFrame: Up to 48 hours post-dose
measure: MOR107 AUC(0-inf) normalised for dose (AUC[0-inf]/D)
timeFrame: Up to 48 hours post-dose
measure: Amount of MOR107 excreted in the urine over a specified period of time after dosing (Ae)
timeFrame: Up to 48 hours post-dose
measure: Cumulative amount of MOR107 excreted in the urine (CumAe)
timeFrame: Up to 48 hours post-dose
measure: Amount of MOR107 excreted in the urine over a specified period of time after dosing, expressed as a percentage of the administered dose (Ae%)
timeFrame: Up to 48 hours post-dose
measure: Cumulative amount of MOR107 excreted in the urine, expressed as a percentage of the administered dose (CumAe%)
timeFrame: Up to 48 hours post-dose
measure: Renal clearance: the apparent volume of plasma cleared per unit time via renal elimination (CLr)
timeFrame: Up to 48 hours post-dose
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
facility: Quotient Clinical
state: Nottinghamshire
Study officials:
affiliation: LanthioPep BV
name: Axel Mescheder, MD
role: STUDY_DIRECTOR
References: