A Phase I Study of the Effects of APF530 Exposure, Granisetron and Moxifloxacin

Study Overview
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Brief Summary
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This Phase I study will be performed in a double-blind, randomized, crossover design in healthy male and female subjects. The central ECG laboratory will be blinded to treatment. Every effort will be made to enroll equal numbers of males and females into the study. Eligible subjects will participate in a screening phase (within 28 days of the dosing day), a treatment phase and a final visit, which will be conducted on discharge from the study. Study duration will be 32 days with a total of approximately 12 days of confinement. During the resting ECG periods, 12-lead digital ECGs will be extracted from continuous telemetry at selected time points to assess potential ECG effects. Blood samples for PK evaluation will be collected in conjunction with the ECG time points.

Official Title
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A Randomized, Placebo-Controlled, Four-Period Crossover Definitive QT Study Of The Effects of APF530 Exposure, High-Dose IV Granisetron and Moxifloxacin on QTc Prolongation

Conditions
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Healthy

Intervention / Treatment
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* Drug: Withdraw treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects in good health aged between 18-50 years weigh at least 50 kg (110 pounds) have a body mass index of 18-32 kg/m2 inclusive capable of understanding and complying with the protocol have signed the informed consent Exclusion Criteria: have a history of drug abuse or are current smokers have a known hypersensitivity to Moxifloxacin or granisetron a history or presence of clinically significant abnormal 12-lead ECG or an ECG with QTc by Bazett's correction of > 450 ms in men, > 470 ms in women on the screening ECG PR > 240 ms, QRS > 110 ms or a history of prolongation of QT interval a family history of Long QT Syndrome or cardiac disease may not have used any medications or consumed any foods contraindicated in the protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| APF530 Exposure, Granisetron and Moxifloxacin, Placebo<br>Arm 1:APF530 Exposure Arm 2:Granisetron IV Arm 3:Moxifloxacin Arm 4:Placebo | Drug: Withdraw treatment<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| QTc Prolongation | To evaluate the effect of APF530 given subcutaneously, in normal volunteers, on placebo subtracted change of QTcF | From baseline over 48 hours. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentrations of granisetron | To achieve a mean Cmax of granisetron and AUC exposure in normal volunteers equivalent to that achieved by APF530 given subcutaneously, in patients. | From baseline over 48 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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QTc Prolongation