A Study to Investigate in Healthy Volunteers (Part 1) and in Patients With Type 2 Diabetes Mellitus (Part 2) the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Doses of RO6799477

This study is designed to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of RO6799477 following once daily oral administration for 2 weeks in healthy volunteers (Part 1) and in Type 2 diabetes patients (T2D) (Part 2). The anticipated time on study treatment is two weeks.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer, Type 2 Diabetes
• Intervention / Treatment: Drug: Placebo; Drug: RO6799477

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Leiden, Netherlands, 2333

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Part 1 Inclusion criteria:

• Right-handed male volunteers
• Aged 18-45 years, inclusive
• Healthy participants, as determined by screening assessments and Principal Investigator's judgment
• Healthy status is defined by the absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead ECG, hematology, blood chemistry, serology and urinalysis
• Body Mass Index (BMI) of 18-30 kg/m2 inclusive, with body weight in the range of 50-100 kg

Part 2 Inclusion Criteria:

• Patients with type 2 diabetes according to WHO criteria diagnosed for at least 3 months prior to screening
• Male or female patients, 40 to 65 years of age, inclusive
• Type 2 diabetic patients who are either drug naive (diet & exercise alone) or on a stable dose of metformin for at least 3 months prior to screening or willing to safely stop sulfonylurea medications at least 2 weeks prior to first dose administration and until follow-up visit
• BMI of 23-42 kg/m2, inclusive

Exclusion Criteria:

Part 1 Exclusion criteria:

• Any clinically relevant history or the presence of e.g. respiratory, renal, hepatic, gastrointestinal, hematological, lymphatic, neurological, cardiovascular, psychiatric, etc. disease or diseases
• Disorders of central nervous system, psychiatric disorders, behavioral disturbances (e.g. cerebrovascular events, depression, post-traumatic stress disorder [PTSD], anxiety, bipolar disorder, severe migraine, Parkinson's disease)
• Participation in an investigational drug or device study within 3 months prior to screening or more than 4 times per year
• Concomitant disease or condition that could interfere with, or treatment of which might interfere with, the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study

Part 2 Exclusion Criteria:

• Type 1 diabetes
• Acquired or secondary forms of diabetes such as those resulting from pancreatic surgery/injury, cystic fibrosis related diabetes
• Evidence or history of clinically significant diabetic complications such as clinically severe diabetic peripheral neuropathy, clinically significant nephropathy as judged by the investigator, or pre-proliferative/proliferative diabetic retinopathy as judged by the investigator or already diagnosed by the diabetologist or general practitioner
• Disorders of central nervous system, psychiatric disorders, behavioral disturbances
• Clinically significant history or presence of bronchopulmonary, gastrointestinal, hematological, lymphatic, neurological, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, infectious, connective tissue or inflammatory diseases, and any type of cancer (with the exception of treated basal cell carcinoma of the skin) or other clinically significant disease
• Use of anti-diabetic drugs other than metformin or sulfonylureas within 2 months prior to screening
• Any condition or disease detected during the medical interview / physical examination that would render the patient unsuitable for the study, place the patient at undue risk or interfere with the ability of the patient to complete the study in the opinion of the investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Part 1: Healthy Volunteers	Drug: Placebo; Matching placebo daily oral administration; Drug: RO6799477; Daily oral administration of RO6799477
EXPERIMENTAL: Part 2: Patients with T2D, Group A; Low dose daily oral administration of RO6799477	Drug: Placebo; Matching placebo daily oral administration; Drug: RO6799477; Daily oral administration of RO6799477
EXPERIMENTAL: Part 2: Patients with T2D, Group B; High dose daily oral administration of RO6799477	Drug: Placebo; Matching placebo daily oral administration; Drug: RO6799477; Daily oral administration of RO6799477

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of adverse events (AEs)	Up to 9 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetic parameters derived from plasma and urine concentrations of RO6799477, area under the concentration time curve (AUC), Cmax	Day 1 and Day 14
Fasting serum glucose	Up to 9 weeks
Fasting serum insulin (Part 2 only)	Up to 9 weeks

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (ACTUAL): December 1, 2014
• Study Completion (ACTUAL): December 1, 2014

Study Registration Dates

• First Submitted: June 6, 2014
• First Submitted That Met QC Criteria: June 12, 2014
• First Posted (ESTIMATE): June 16, 2014

Study Record Updates

• Last Update Posted (ACTUAL): June 14, 2017
• Last Update Submitted That Met QC Criteria: June 13, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: BP29205; 2014-000718-78 (EUDRACT_NUMBER)