Clinical trial NCT02524782: A Phase 1, Single- and Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of MEDI4166 in Subjects With Type 2 Diabetes
Official title: A Phase 1, Combined Single- and Multiple-ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), and Pharmacodynamics (PD) of MEDI4166 in Subjects With Type 2 Diabetes Mellitus (T2D)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type 2 Diabetes
Keywords: MEDI-4166, diabetes
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2015-08-17
Enrollment: 103
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A Phase 1, combined Single Ascending Dose (SAD) and Multiple-ascending Dose (MAD) study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of MEDI4166 in Subjects with Type 2 Diabetes Mellitus (T2D).

Detailed description: This study is a first time in human (FTIH), Phase 1, randomized, double-blind study to evaluate the safety, tolerability, PK, and PD of MEDI4166 administered as both single and multiple ascending doses to subjects with T2D.

Eligibility criteria: Inclusion Criteria:

* Type 2 Diabetes, ages 18-65
* Must provide written informed consent
* BMI\>=25 and =\<42
* Venous access suitable for multiple cannulations
* Vital signs within normal specified ranges
* Females must be non-lactating and non-childbearing potential
* Males must practice 2 effective contraceptive measures if sexually active

Exclusion Criteria:

* Any concurrent condition that in the opinion of the investigator would interfere with the evaluation of the investigational product
* History or presence of gastrointestinal, renal, or hepatic disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs
* History of cancer, with the exception of basal cell carcinoma or carcinoma of the cervix
* Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks prior to dosing
* Positive Hepatitis B, Hepatitis C or HIV test or use of antiretroviral medications at screening
* Current or previous use of systemic corticosteroids within the past 28 days prior to screening
* Use of any medicinal products or herbal preparations licensed for weight loss is prohibited.
* Positive drug screen
* Type 1 diabetes

Primary outcomes:
measure: Part A: Number of subjects with adverse events as a measure of safety and tolerability of MEDI4166
timeFrame: 43 days post dosing
measure: Part A: Number of subjects with adverse events as a measure of safety and tolerability of MEDI4166
timeFrame: 43 days post dosing
measure: Part A: Number of subjects with adverse events as a measure of safety and tolerability of MEDI4166
timeFrame: 43 days post dosing
measure: Part A: Number of subjects with adverse events as a measure of safety and tolerability of MEDI4166
timeFrame: 43 days post dosing
measure: Part A: Number of subjects with adverse events as a measure of safety and tolerability of MEDI4166
timeFrame: 43 days post dosing
measure: Part B: Change in glucose AUC measured up to 240 minutes after mixed meal tolerance test (MMTT) from baseline to Day 36
timeFrame: 36 days post dosing
measure: Part B: Change in LDL-C from baseline to Day 36
timeFrame: 36 days post dosing
Secondary outcomes:
measure: Part A: Pharmacokinetics of MEDI4166, maximum plasma concentration (Cmax)
timeFrame: 43 days post dosing
measure: Part A: Pharmacokinetics of MEDI4166, area under the curve concentration (AUC)
timeFrame: 43 days post dosing
measure: Part A: Change from baseline in LDL-C
timeFrame: 43 days post dosing
measure: Part A: Proportion of subjects with Anti-drug Antibodies (ADA) to MEDI4166
timeFrame: 43 days post dosing
measure: Part B: Number of subjects with adverse events as a measure of safety and tolerability of MEDI4166
timeFrame: 71 days post dosing
measure: Part B: Number of subjects with adverse events as a measure of safety and tolerability of MEDI4166
timeFrame: 71 days post dosing
measure: Part B: Number of subjects with adverse events as a measure of safety and tolerability of MEDI4166
timeFrame: 71 days post dosing
measure: Part B: Number of subjects with adverse events as a measure of safety and tolerability of MEDI4166
timeFrame: 71 days post dosing
measure: Part B: Number of subjects with adverse events as a measure of safety and tolerability of MEDI4166
timeFrame: 71 days post dosing
measure: Part B: Pharmacokinetics of MEDI4166, maximum plasma concentration (Cmax)
timeFrame: 71 days post dosing
measure: Part B: Pharmacokinetics of MEDI4166, area under the curve concentration (AUC)
timeFrame: 71 days post dosing
measure: Part B: Change from baseline in fructosamine levels
timeFrame: 36 days post dosing
measure: Part B: Proportion of subjects with ADA to MEDI4166
timeFrame: 71 days post dosing
measure: Part A: Pharmacokinetics of MEDI4166, time to maximum observed plasma drug concentration (Tmax)
timeFrame: 43 days post dosing
measure: Part A: Change from baseline in glucose AUC up to 240 minutes
timeFrame: 43 days post dosing
measure: Part B: Pharmacokinetics of MEDI4166, time to maximum observed plasma drug concentration (Tmax)
timeFrame: 71 days post dosing
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Research Site
state: Alabama
city: Chula Vista
country: United States
facility: Research Site
state: California
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: South Miami
country: United States
facility: Research Site
state: Florida
city: Durham
country: United States
facility: Research Site
state: North Carolina
city: Raleigh
country: United States
facility: Research Site
state: North Carolina
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Knoxville
country: United States
facility: Research Site
state: Tennessee
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
Study officials:
References:
citation: Jain M, Carlson G, Cook W, Morrow L, Petrone M, White NE, Wang T, Naylor J, Ambery P, Lee C, Hirshberg B. Randomised, phase 1, dose-finding study of MEDI4166, a PCSK9 antibody and GLP-1 analogue fusion molecule, in overweight or obese patients with type 2 diabetes mellitus. Diabetologia. 2019 Mar;62(3):373-386. doi: 10.1007/s00125-018-4789-6. Epub 2018 Dec 28.