A Two-part, Single-dose, Randomized Study to Evaluate the Safety of Supra-therapeutic Doses of RO7033877 and to Investigate the Effect of RO7033877 on the QTc Interval

November 1, 2016 updated by: Hoffmann-La Roche

A Two-part, Single-center, Single-dose, Randomized, Double-blind, Double-dummy, Placebo-controlled, Positive-controlled, Four-way Crossover Study to Investigate the Effect of RO7033877 on the QT/QTc Interval in Healthy Subjects

This is a two-part study to evaluate the safety and tolerability of supratherapeutic doses of RO7033877 (Part 1) and to investigate the effect of RO7033877 on the QTc interval in healthy volunteers (Part 2). Part 1 is a single ascending dose, randomized, observer-blind, placebo-controlled study to determine the safety tolerability and pharmacokinetics of a supratherapeutic dose to be used in Part 2. Participants will be randomized in up to 8 cohorts to receive a single dose of either RO7033877 or placebo. Part 2 will be a single dose, randomized, double-blind, double dummy, placebo-controlled, positive control, 4-way crossover study. Part 2 will evaluate whether a single therapeutic or supratherapeutic dose of RO7033877 has a threshold pharmacologic effect on cardiac repolarization, as detected by changes in the QT/QTc interval measured by electrocardiogram (ECG). Pharmacokinetic parameters will be assessed for Parts 1 and 2, continuous ECG recordings will be evaluated in Part 2.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
64

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Healthy male or female of non-childbearing potential participants, 18 to 65 years of age, inclusive
  • Healthy status is defined as the absence of evidence of any clinically significant, active, or chronic disease following a detailed medical and surgical history, a complete physical examination and vital signs, 12-lead ECG, hematology, blood chemistry, serology and urinalysis and confirmed by a creatinine clearance estimated by formula of Cockcroft-Gault > 80 mL/min/1.73 m2
  • Postmenopausal or surgically sterile females (bilateral oophorectomy or hysterectomy performed at least 6 months prior to study participation)
  • A body mass index (BMI) between 18 and 30 kg/m2 inclusive and minimum body weight >/= 50 kg, inclusive
  • For men with a female partner(s) of childbearing potential: agreement to use a barrier method of contraception during the treatment period and for at least 3 months after the last dose of study drug
  • Participants who are non-smokers, or former smokers who have not smoked for at least 45 days prior to screening (former smokers are to have a total of < 10 pack year smoking history)

Exclusion Criteria:

  • Women of childbearing potential
  • Pregnant or lactating women
  • Men with female partners who are lactating or are pregnant
  • History of any clinically significant disease, e.g. gastrointestinal, renal, hepatic, cardiovascular, endocrine, hematologic or allergic disease(s), metabolic disorder, cancer (may have had basal or squamous cell carcinoma of skin or cervix as long as surgically removed or deemed cured by cryotherapy, laser therapy, conization, etc., with stability for the past 2 years)
  • Any major illness within one month before the first dose of study drug or any febrile illness within one week prior to screening and up to first dose administration
  • Any prescribed medications taken within 4 weeks prior to first dosing or within 5 times the elimination half-life of the medication prior to first dosing (whichever is longer)
  • Any preparations containing St. John's Wort taken within 4 weeks prior to first dosing
  • Any other over-the-counter medications, including vitamins or herbal remedies, taken within 14 days prior to first dosing or within 5 times the elimination half-life of the medication prior to first dosing (whichever is longer); acetaminophen is the only exception
  • Taking any nutrients known to modulate cytochrome P450 (CYP) 3A activity. Participants will be instructed to abstain from consuming grapefruit, Seville oranges, and grapefruit- or Seville orange-containing products within 2 weeks prior to administration of study drugs
  • Regular consumption of large amounts of caffeine or xanthine-containing substances (e.g. >/= 5 cups of coffee/day, tea, cola, Mountain Dew, chocolate, diet pills, "energy drinks" or any other type of stimulant) or unable to refrain from consumption of caffeine or xanthine-containing substances from 72 hours prior to each entry in the clinic and during the in-house periods
  • Any medication that inhibits active tubular secretion (e.g. probenecid, H2 receptor antagonists, trimethoprim) within 4 weeks prior to first dosing
  • Participation in an investigational drug or device study within 60 days prior to screening
  • 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
  • History and/or family history of cardiac anomalies, e.g. congenital long QT syndrome, unexplained syncope, or clinically significant abnormal ECG
  • ECG evidence at screening or baseline of, e.g. atrial fibrillation, atrial flutter, complete right or left bundle branch block and/or clinically relevant prolongation of the PR interval as determined by the Investigator

Exclusion criteria for Part 2 only:

  • History of allergy or sensitivity to moxifloxacin or other fluoroquinolones, and/or history of tendon rupture when taking or considered time-wise related to consumption of a fluoroquinolone

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Part 1: Placebo
Saline solution, given as a minimum of a 2 hour infusion
Drug: Part 1: SAD placebo
Single dose
Experimental: Part 1: RO7033877
Single ascending dose
Drug: Part 1: SAD RO7033877
Single dose
Experimental: Part 2: RO7033877
Single-dose 4-way crossover
Drug: Part 2: Treatment A, RO7033877
Single dose RO7033877 and moxifloxacin placebo
Drug: Part 2: Treatment B, RO7033877
Single dose RO7033877 and moxifloxacin placebo
Drug: Part 2: Treatment C, moxifloxacin
Single dose moxifloxacin and RO7033877 placebo
Drug: Part 2: Treatment D, RO7033877 and moxifloxacin placebo
Single dose moxifloxacin placebo and RO7033877 placebo

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Part 1: Incidence of adverse events (AEs) after single, supratherapeutic dose of RO7033877
Time Frame: Up to 30 days
Up to 30 days
Part 1: Pharmacokinetic parameters derived from plasma and urine concentrations, single dose of RO7033877: Area under the curve (AUC)
Time Frame: Day 1
Day 1
Part 2: Continuous, 12-lead Holter electrocardiogram (ECG) recordings
Time Frame: Day -1 and 1 of each Period
Day -1 and 1 of each Period

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Incidence of AEs after single IV infusion of RO7033877
Time Frame: Up to 9 weeks
Up to 9 weeks
Part 2 only: Changes in other ECG parameters, descriptive analysis
Time Frame: Up to 9 weeks
Up to 9 weeks
Part 2 only: Changes in PK/PD relationships between any effect on ECG and RO7033877 plasma concentrations, descriptive analysis
Time Frame: Up to 9 weeks
Up to 9 weeks
Part 2: Area under the concentration-time curve (AUC) of RO7033877
Time Frame: Day 1 of each Period
Day 1 of each Period

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hoffmann-La Roche

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 1, 2014

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 13, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 16, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 17, 2014

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 2, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 1, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NP29334

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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