A randomized, double-blind, placebo-controlled study in two parts to investigate in Part 1 the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple ascending dose of RO6799477 in healthy volunteers, and in Part 2 the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple dose of RO6799477 in patients with type 2 diabetes mellitus.

A randomized, double-blind, placebo-controlled study in two parts to investigate in Part 1 the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple ascending dose of RO6799477 in healthy volunteers, and in Part 2 the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple dose of RO6799477 in patients with type 2 diabetes mellitus. - Research into the effects of RO6799477 during a longer period

Status

Active, not recruiting

Phases

Unknown

Study type

Interventional

Source

NL-OMON

Registry ID

NL-OMON40841

Enrollment

Registered

2014-06-02

Start date

2014-06-19

Completion date

Unknown

Last updated

2024-04-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Mood disorders Mood disorders Schizophrenia

Interventions

RO6799477 capsules (using combinations of 10 and 100 mg dosage strengths). Part 1 In each cohort, subjects will receive daily oral administration of RO6799477 or placebo for 14 days as in-clinic. Ten

3 placebo). For all the treatment groups, the same number of capsules (mix of matching placebo capsules and capsules of RO6799477 to obtain the chosen dose) will be taken daily to ensure blinding. T

Eligibility

Age

18 Years to 99 Years

Inclusion criteria

Inclusion criteria: Part 1: healthy right-handed male subjects 18 to 45 years of age, inclusive. Part 2: male and female patients with type 2 diabetes, 40 to 65 years of age, inclusive.

Exclusion criteria

Exclusion criteria: (see page 50 of the protocol for the complete list) Part 1:;Disorders of central nervous system, psychiatric disorders;;Suicidal or homicidal risk, or history of suicide;;Personal or familial history (1st degree) of seizures, epilepsy or other convulsive condition;;Family history (1st degree) of psychosis or mood disorders;;Contraindications for MRI scans;;Contraindications for lumbar puncture; ;History or presence of clinically significant ECG abnormalities;;Angle closure glaucoma, history or current significant ophthalmologic or neurologic condition adversely affecting the pupillometry assessment.;Part 2:;Type 1 diabetes and acquired or secondary forms of diabetes, history of acute metabolic complications (diabetic ketoacidosis or hyperosmolar hyperglycaemia);;Evidence or history of clinically significant diabetic complications such as clinically severe diabetic peripheral neuropathy, nephropathy, pre-proliferative/proliferative diabetic retinopathy;;History of severe symptomatic hypoglycaemia within 6 months prior to screening;;History of weight loss surgery or gastric bypass, gastric stapling, or gastric banding or any other bariatric surgical procedure;;History of eating disorder (e.g., anorexia nervosa and bulimia);;Disorders of central nervous system, psychiatric disorders;;Suicidal or homicidal risk, or history of suicide;;Personal or familial history (1st degree) of seizures, epilepsy or other convulsive condition;;Family history (1st degree) of psychosis or mood disorders;;History or presence of clinically significant ECG abnormalities;;Angle closure glaucoma, history or current significant ophthalmologic or neurologic condition adversely affecting the pupillometry assessment.

Design outcomes

Primary

Measure	Time frame
PHARMACOKINETIC OUTCOME MEASURES Parts 1 and 2: Plasma and urine concentrations of RO6799477 will be measured by a specific and validated LC-MS/MS method. The following pharmacokinetic parameters will be estimated using standard non-compartmental methods. Day 1 and Day 14: Cmax, tmax, AUC0-* and AUCinf (as appropriate), z, t, CL/F, Ae and CLR. Steady state achievement: Ctrough. Accumulation: RAUC, RCmax, RCtrough. Pooled plasma samples will also be used for exploratory RO6799477 metabolite identification. In Part 1 of the study, blood samples for PK analysis will be drawn before dosing (trough samples as specified in SoA) and immediately (within 30 minutes) before start of the fMRI scan. Part 1 only: Population pharmacokinetic (PPK) parameters estimated by non-linear modeling on the CSF concentration-time profiles obtained by applying a sparse sampling strategy. PHARMACODYNAMIC OUTCOME MEASURES Glycemic parameters: o Fasting serum glucose o Prolactin levels o Fasting serum insulin (Part 2 only) • Glycemic blood profiles (Part 2 only): o 24-h glucose profile (serum) o 24-h insulin profile (serum). • Meal tolerance test (MTT): • Hemoglobin A1c (HbA1c) and fasting serum fructosamine (Part 2 only). • Scales for appetite sensation: CNS questionnaire: Self-rating scales at specified timepoints o Profile of Mood State (POMS): o ARCI-49 questionnaire (for sedation and dysphoria): o Columbia Suicide-Severity Rating Scale (C-SSRS) (detection of potential for suicidality) • Pupillometry: • Functional magnetic resonance imaging (fMRI) in Part 1 only.	—

Measure

Time frame

PHARMACOKINETIC OUTCOME MEASURES Parts 1 and 2: Plasma and urine concentrations of RO6799477 will be measured by a specific and validated LC-MS/MS method. The following pharmacokinetic parameters will be estimated using standard non-compartmental methods. Day 1 and Day 14: Cmax, tmax, AUC0-* and AUCinf (as appropriate), *z, t*, CL/F, Ae and CLR. Steady state achievement: Ctrough. Accumulation: RAUC, RCmax, RCtrough. Pooled plasma samples will also be used for exploratory RO6799477 metabolite identification. In Part 1 of the study, blood samples for PK analysis will be drawn before dosing (trough samples as specified in SoA) and immediately (within 30 minutes) before start of the fMRI scan. Part 1 only: Population pharmacokinetic (PPK) parameters estimated by non-linear modeling on the CSF concentration-time profiles obtained by applying a sparse sampling strategy. PHARMACODYNAMIC OUTCOME MEASURES Glycemic parameters: o Fasting serum glucose o Prolactin levels o Fasting serum insulin (Part 2 only) • Glycemic blood profiles (Part 2 only): o 24-h glucose profile (serum) o 24-h insulin profile (serum). • Meal tolerance test (MTT): • Hemoglobin A1c (HbA1c) and fasting serum fructosamine (Part 2 only). • Scales for appetite sensation: CNS questionnaire: Self-rating scales at specified timepoints o Profile of Mood State (POMS): o ARCI-49 questionnaire (for sedation and dysphoria): o Columbia Suicide-Severity Rating Scale (C-SSRS) (detection of potential for suicidality) • Pupillometry: • Functional magnetic resonance imaging (fMRI) in Part 1 only.

—

Countries

Netherlands

Outcome results

None listed

Source: NL-OMON (via WHO ICTRP)