Study to Assess Safety, Tolerability and Phamacokinetics of KAE609 Administered Intravenously in Healthy Subjects

Novartis Pharmaceuticals57 enrolled

Overview

This was a randomized, subject and investigator-blinded, placebo-controlled, single and multiple ascending intravenous (iv) dose study in healthy subjects to assess the safety and tolerability of KAE609 given in the vein.

The study consisted of 2 parts: single-ascending dose (SAD) part and multiple ascending dose (MAD) part. In Part A (Single-ascending dose (SAD) part), it was planned to recruit 6 active, 2 placebo subjects in each cohort: * Cohort A1: 10.5 mg/placebo * Cohort A2: 30 mg/placebo * Cohort A3: 75 mg/placebo * Cohort A4: 120 mg/placebo * Cohort A5: 210 mg/placebo In Part B (Multiple-ascending dose (MAD) part), Subjects were assigned to one of the following treatment arms in a ratio of 2:1 (6 active, 3 placebo): * Cohort B1: 60 mg/placebo, every 24 hours (q24h) × 5 days * Cohort B2: 120 mg/placebo, every 24 hours (q24h) × 5 days Eligible subjects were randomized to receive a single or q24h x 5 doses of either KAE609 or placebo. Safety, tolerability and pharmacokinetics were assessed over the period of 8 days for single dose and 12 days for multiple dose up to end of study visit for each subject.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

OTHER

Masking

DOUBLE

Enrollment

Conditions

Malaria

Interventions

KAE609DRUG

* iv bolus administration over approximately 2 min for doses \< 75 mg (Cohorts A1, A2 and B1) * iv infusion over approximately 10 min for doses ≥ 75 mg (Cohorts A3, A4, A5 and B2)

PlaceboDRUG

matching placeo for iv administration

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

Key Inclusion Criteria: * Healthy male and female subjects 18 to 55 years of age inclusive, and in good health as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests. * Subjects must weigh at least 50 kg to participate in the study, and must have a body mass index (BMI) within the range of 18.0 - 30.0 kg/m2. Key Exclusion Criteria: * Use of other investigational drugs within 5 half-lives of Screening, or within 30 days of dosing, whichever is longer; or longer if required by local regulations. * Significant illness which has not resolved within two (2) weeks prior to initial dosing. * Pregnant or nursing (lactating) women. * Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant. * Sexually active males unwilling to use a condom during intercourse while taking investigational drug and for at least 2 weeks after last dose of investigational drug.

Locations (1)

Novartis Investigative Site

Antwerp, Belgium

Outcomes

Primary Outcomes

Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Deaths

The distribution of adverse events was done via the analysis of frequencies for Adverse Event (AEs), Serious Adverse Event (SAEs) and Deaths, through the monitoring of relevant clinical and laboratory safety parameters.

Time frame: From study treatment start date till 30 days safety follow-up, assessed for up to 4 months

Secondary Outcomes

Part A - Pharmacokinetic of KAE609: Maximum Observed Plasma Concentration (Cmax)

Venous whole blood samples were collected for activity-based pharmacokinetics characterization. Cmax was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.