Effect of a Single Oral Dose of Moxidectin on the Cardiac QT Interval of Healthy Volunteers

NCT03012828 | Completed Phase 1 Results

• 1 other identifier: MDGH-MOX-1008
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This study will investigate the effect of a single oral dose of moxidectin on the QT interval associated with moxidectin plasma concentrations. The effect of moxidectin on other ECG intervals, and on safety, will also be assessed, as will preliminary pharmacokinetics and metabolism

Conditions

QT Effects in Healthy Volunteers

Outcome Measures

Primary Outcomes (1)

• Mean Change From Baseline in QTc Interval (Corrected by Friderica's Formula, dQTcF) Associated With Plasma Moxidectin Concentrations After a Single Dose

  Triplicate 10-second ECG recordings taken 1 minute apart using a Mortara continuous 12-lead digital ECG recorder connected to each subject during the Baseline to 72-hour post dose confinement period. Baseline only and baseline and placebo adjusted changes in QTc interval (corrected using the Friderica formula, QTcF) at each timepoint for each dose level were determined. The mean change from baseline (without and with placebo correction, dQTcF and ddQTcF respectively) at each of the 14 time points was calculated for each dose level. The primary outcome measure was the mean dQTcF for all subjects(the dQTcF gradient). The mean dQTcF for each active treatment group was determined at each post dose timepoint but the mean dQTcF by dose level was not calculated. The mean dQTcF at approximate moxidectin Tmax (hour 3 or hour 4) for each active treatment group and at hour 3 for the placebo group is reported.

  Baseline (pre-dose) and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 60, and 72 hours post dosing

Secondary Outcomes (1)

• Concentrations of Moxidectin in Plasma

  Pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12*, 24, 36, 48, 60, and 72 hours and days 8,15 and 22 post dosing

Other Outcomes (2)

• Subjects With Categorical Changes From Baseline in 12-lead Electrocardiograms (ECGs)

  At Baseline and Days 1, 2, 3, 4, 22 and Week 12

• Change From Baseline in Heart Rate (HR) and Duration of Other Interval Parameters (PR and QRS)

  Baseline (pre-dose) and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 60, and 72 hours post dosing

Study Arms (6)

Moxidectin 4mg

EXPERIMENTAL

10 subjects will receive a single oral dose of moxidectin 4mg

Drug: Moxidectin

Moxidectin 8mg

EXPERIMENTAL

10 subjects will receive a single oral dose of moxidectin 8mg

Drug: Moxidectin

Moxidectin 16mg

EXPERIMENTAL

10 subjects will receive a single oral dose of moxidectin 16mg

Drug: Moxidectin

Moxidectin 24mg

EXPERIMENTAL

10 subjects will receive a single oral dose of moxidectin 24mg

Drug: Moxidectin

Moxidectin 36mg

EXPERIMENTAL

10 subjects will receive a single oral dose of moxidectin 36mg

Drug: Moxidectin

Placebo

PLACEBO COMPARATOR

10 subjects will receive a single oral dose of placebo

Other: Placebo

Interventions

Moxidectin DRUG

Moxidectin is a broad spectrum macrocyclic lactone endectocide

Moxidectin 16mg; Moxidectin 24mg; Moxidectin 36mg; Moxidectin 4mg; Moxidectin 8mg

Placebo OTHER

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male between 18 and 50 years of age (inclusive);
• Body mass index (BMI) of 18 to 30 kg/m2 (inclusive) and a minimum weight of 50 kg (110 lbs);
• Biologically or surgically sterile or must commit to using a reliable method of birth control, in the opinion of the investigator, from Screening through the duration of the study;
• Willing and able to give written informed consent.

You may not qualify if:

• Unwilling to abstain from alcohol, caffeine, xanthine containing products, Seville oranges, grapefruit juices, and fish liver oils within 72 hours before Check in (Day -1) and throughout the inpatient period of the study;
• Less than 1 bowel movement every 24 hours in the absence of any laxative, suppository, or enema use during the month before Screening;
• Abnormal fecal consistency within 24 hours of Check in (Day -1);
• Clinically relevant abnormal findings on medical history, clinical laboratory test results, vital sign measurements, safety 12 lead ECG results, or physical examination at Screening or Baseline which, in the opinion of the investigator, would interfere with dosing, jeopardize the safety of the subject, or impact the validity of the study results;
• History of clinically significant dermatologic, gastrointestinal, renal, hepatic, neurologic, hematologic, endocrine, oncologic, pulmonary, immunologic, psychiatric, or cardiovascular disease or any other condition which, in the opinion of the investigator, would interfere with dosing, jeopardizes the safety of the subject, or impacts the validity of the study results;
• History or hypersensitivity or allergic reactions to ivermectin, moxidectin, or any of the ingredients in the study drug as described in the Investigator's Brochure;
• Any condition that may affect oral drug absorption (eg, previous surgery on the gastrointestinal tract including removal of parts of the stomach, bowel, liver, gall bladder, or pancreas);
• History of risk factors for torsades de pointes, including unexplained syncope, known long QT syndrome, heart failure, myocardial infarction, angina, or clinically significant abnormal laboratory assessments including hypokalemia, hypercalcemia, or hypomagnesemia. Subjects are also excluded if there is a family history of long QT syndrome or Brugada syndrome;
• A sustained supine systolic blood pressure \>150 mm Hg or \<90 mm Hg or a supine diastolic blood pressure \>95 mm Hg or \<50 mm Hg at Screening or Check in (Day -1). Blood pressure may be retested twice in the supine position. The blood pressure abnormality is considered sustained if either the systolic or the diastolic blood pressure values are outside of the stated limits after 3 assessments, and the subject will not to be randomized;
• A resting heart rate (HR) of \<40 beats per minute (bpm) or \>100 bpm when vital signs are measured at Screening or Check in (Day -1);
• An uninterpretable or abnormal screening ECG indicating a second or third degree atrioventricular block, or 1 or more of the following: QRS interval \>110 milliseconds (msec); QT interval corrected by Fridericia's formula (QTcF) \>450 msec; PR interval \>200 msec; or any rhythm other than sinus rhythm that is interpreted by the investigator to be clinically significant;
• Concomitant use of prescription medications, including medications known to prolong the corrected QT interval (QTc) or herbal preparations, within 14 days or 5 half-lives (whichever is longer) before study drug dosing, or use of an over the counter (OTC) medication or vitamins within 7 days before study drug dosing;
• Received an investigational drug during the 30 days, or 5 half lives of the study drug (whichever is longer), before Check in (Day -1) or is planning to receive another investigational drug at any time during the study;
• History or presence of alcohol abuse (defined as consumption of more than 210 mL of alcohol per week, or the equivalent of fourteen 4 ounce \[oz\] glasses of wine or fourteen 12 oz cans/bottles of beer or wine coolers per week) within 6 months before Screening or positive alcohol test at Screening or Check-in (Day -1);
• History or presence of substance abuse within the past 2 years or positive drug screen test at Screening or Check in (Day -1);

Sponsors & Collaborators

• Medicines Development for Global Health: lead

Study Sites (1)

Spaulding Clinical

West Bend, Wisconsin, 53095, United States

Location

Related Publications (1)

• Kinrade SA, Mason JW, Sanabria CR, Rayner CR, Bullock JM, Stanworth SH, Sullivan MT. Evaluation of the Cardiac Safety of Long-Acting Endectocide Moxidectin in a Randomized Concentration-QT Study. Clin Transl Sci. 2018 Nov;11(6):582-589. doi: 10.1111/cts.12583. Epub 2018 Sep 19.

  PMID: 30117300 DERIVED

MeSH Terms

Interventions

moxidectin

Results Point of Contact

• Title: Sally Kinrade, Vice President (Clinical Development)
• Organization: Medicines Development Limited

sally.kinrade@medicinesdevelopment.com

+613 9629 6111

Study Officials

• Mark Sullivan

  Sponsor GmbH

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2016
• First Posted: January 6, 2017
• Study Start: January 1, 2017
• Primary Completion: March 1, 2017
• Study Completion: May 1, 2017
• Last Updated: March 14, 2019
• Results First Posted: March 14, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)