Cardiac Safety Evaluation of P03277

Guerbet

Status and phase: Completed; Phase 1

Conditions: Healthy Volunteers

Treatments: Drug: P03277 0.3 mmol/kg; Drug: Moxifloxacin 400mg; Drug: P03277 0.1 mmol/kg; Drug: NaCl 0.9%

Study type: Interventional

Funder types: Industry

Identifiers

NCT03657264

GDX-44-006

Details and patient eligibility

About

The study is a Phase I, Single center, Randomized, Cross-over Double-blind Placebo-controlled and Open-label Positive-controlled (moxifloxacin) in healthy volunteers.

The primary objective is to assess the cardiac safety after administration of P03277 to 48 healthy volunteers at dose of 0.1 mmol/kg (anticipated clinical dose) and 0.3 mmol/kg (supra-clinical dose) by evaluating the QT and QTc intervals.

Full description

Each subjects will be administered with 4 products (P03277 at the 2 different doses, placebo and moxifloxacin) in a 4*4 cross over sequence balanced for first order carry over effect. Twelve subjects will be assigned to each sequence (6 males and 6 females). The volunteers will be enrolled sequentially by cohort of 8 subjects.

ECG measurements will be compared with ECG parameters collected after administration of placebo (Nacl 0.9%). The test sensitivity will be assessed using a positive control (moxifloxacin 400 mg per os) known to induce delays in QT intervals.

Enrollment: 48 patients

Sex: All

Ages: 18 to 59 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Subject assessed as healthy by a comprehensive clinical assessment (detailed medical history and complete physical examination)
• Subject with a Body Mass Index (BMI) > 19 kg/m² and < 28 kg/m² and a weight at least of 40 kg for female and 50 kg for male and at maximum of 100 kg

Exclusion criteria

Trial design

Primary purpose: Diagnostic

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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48 participants in 4 patient groups

Sequence 1

Experimental group

Description:

The sequence of administration is: P/ScD/PC/CD Where: * P = Placebo (Nacl 0.9%) * CD = P03277 tested at 0.1 mmol/kg * ScD = P03277 tested at 0.3 mmol/kg * PC = Positive control (moxifloxacin 400 mg - per os).

Treatment:

Drug: Moxifloxacin 400mg

Drug: P03277 0.1 mmol/kg

Drug: NaCl 0.9%

Drug: P03277 0.3 mmol/kg

Sequence 2

Experimental group

Description:

The sequence of administration is: CD/PC/ScD/P Where: * P = Placebo (Nacl 0.9%) * CD = P03277 tested at 0.1 mmol/kg * ScD = P03277 tested at 0.3 mmol/kg * PC = Positive control (moxifloxacin 400 mg - per os).

Treatment:

Drug: Moxifloxacin 400mg

Drug: P03277 0.1 mmol/kg

Drug: NaCl 0.9%

Drug: P03277 0.3 mmol/kg

Sequence 3

Experimental group

Description:

The sequence of administration is: ScD/CD/P/PC Where: * P = Placebo (Nacl 0.9%) * CD = P03277 tested at 0.1 mmol/kg * ScD = P03277 tested at 0.3 mmol/kg * PC = Positive control (moxifloxacin 400 mg - per os).

Treatment:

Drug: Moxifloxacin 400mg

Drug: P03277 0.1 mmol/kg

Drug: NaCl 0.9%

Drug: P03277 0.3 mmol/kg

Sequence 4

Experimental group

Description:

The sequence of administration is: PC/P/CD/ScD Where: * P = Placebo (Nacl 0.9%) * CD = P03277 tested at 0.1 mmol/kg * ScD = P03277 tested at 0.3 mmol/kg * PC = Positive control (moxifloxacin 400 mg - per os).

Treatment:

Drug: Moxifloxacin 400mg

Drug: P03277 0.1 mmol/kg

Drug: NaCl 0.9%

Drug: P03277 0.3 mmol/kg