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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03012828
Recruitment Status : Completed
First Posted : January 6, 2017
Results First Posted : March 14, 2019
Last Update Posted : March 14, 2019
Sponsor:
Information provided by (Responsible Party):
Medicines Development for Global Health

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition QT Effects in Healthy Volunteers
Interventions Drug: Moxidectin
Other: Placebo
Enrollment 60
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Moxidectin 4mg Moxidectin 8mg Moxidectin 16mg Moxidectin 24mg Moxidectin 36mg Placebo
Hide Arm/Group Description

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

Moxidectin

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

Moxidectin

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

Moxidectin

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

Moxidectin

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

Moxidectin

10 subjects will receive a single oral dose of placebo

Placebo

Period Title: Overall Study
Started 10 10 10 10 10 10
Completed 9 10 8 10 8 8
Not Completed 1 0 2 0 2 2
Reason Not Completed
Lost to Follow-up             1             0             1             0             1             0
Withdrawal by Subject             0             0             1             0             0             1
Non-compliance with protocol             0             0             0             0             1             0
Delay to last visit would delay DBL             0             0             0             0             0             1
Arm/Group Title Moxidectin 4mg Moxidectin 8mg Moxidectin 16mg Moxidectin 24mg Moxidectin 36mg Placebo Total
Hide Arm/Group Description

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

Moxidectin

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

Moxidectin

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

Moxidectin

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

Moxidectin

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

Moxidectin

10 subjects will receive a single oral dose of placebo

Placebo

Total of all reporting groups
Overall Number of Baseline Participants 10 10 10 10 10 10 60
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 10 participants 10 participants 10 participants 10 participants 10 participants 10 participants 60 participants
37.1  (7.77) 30.4  (8.73) 30.9  (8.32) 31.2  (8.27) 30.2  (8.87) 32.3  (6.72) 32.0  (8.15)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 10 participants 10 participants 10 participants 10 participants 10 participants 60 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Male
10
 100.0%
10
 100.0%
10
 100.0%
10
 100.0%
10
 100.0%
10
 100.0%
60
 100.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 10 participants 10 participants 10 participants 10 participants 10 participants 60 participants
Hispanic or Latino
2
  20.0%
2
  20.0%
1
  10.0%
1
  10.0%
0
   0.0%
0
   0.0%
6
  10.0%
Not Hispanic or Latino
8
  80.0%
8
  80.0%
9
  90.0%
9
  90.0%
10
 100.0%
10
 100.0%
54
  90.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 10 participants 10 participants 10 participants 10 participants 10 participants 60 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
1
  10.0%
0
   0.0%
1
  10.0%
0
   0.0%
2
   3.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  10.0%
0
   0.0%
1
   1.7%
Black or African American
3
  30.0%
7
  70.0%
4
  40.0%
5
  50.0%
5
  50.0%
5
  50.0%
29
  48.3%
White
7
  70.0%
3
  30.0%
5
  50.0%
4
  40.0%
3
  30.0%
5
  50.0%
27
  45.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
1
  10.0%
0
   0.0%
0
   0.0%
1
   1.7%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 10 participants 10 participants 10 participants 10 participants 10 participants 10 participants 60 participants
10 10 10 10 10 10 60
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kilogram /meter squared (kg/m2)
Number Analyzed 10 participants 10 participants 10 participants 10 participants 10 participants 10 participants 60 participants
26.2  (3.74) 24.9  (3.35) 25.8  (3.71) 25.1  (3.00) 26.7  (3.09) 26.1  (3.11) 25.8  (3.26)
1.Primary Outcome
Title Mean Change From Baseline in QTc Interval (Corrected by Friderica's Formula, dQTcF) Associated With Plasma Moxidectin Concentrations After a Single Dose
Hide Description 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.
Time Frame Baseline (pre-dose) and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 60, and 72 hours post dosing
Hide Outcome Measure Data
Hide Analysis Population Description
The ECG population included all subjects who received one dose of study drug and have at least 1 pair of pre-dose and post-dose QTc interval and was used in the model.
Arm/Group Title Moxidectin 4mg Moxidectin 8mg Moxidectin 16mg Moxidectin 24mg Moxidectin 36mg Placebo All Subjects
Hide Arm/Group Description:

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

Moxidectin

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

Moxidectin

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

Moxidectin

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

Moxidectin

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

Moxidectin

10 subjects will receive a single oral dose of placebo

Placebo

50 subjects received a single dose of between 4mg and 36mg of moxidectin. 10 subjects received a dose of placebo,
Overall Number of Participants Analyzed 10 10 10 10 10 10 60
Mean (90% Confidence Interval)
Unit of Measure: millseconds
-5.1
(-10.90 to 0.68)
-4.5
(-9.19 to 0.27)
-4.5
(-8.39 to -0.63)
-6.3
(-12.68 to 0.04)
-3.9
(-7.77 to 0.03)
-2.9
(-6.58 to 0.76)
-0.0077
(-0.0255 to 0.0101)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection All Subjects
Comments The primary analysis used a mixed-effects model to explore the relationship between the time-matched, baseline-adjusted QTcF (delta (d)QTcF) and moxidectin concentrations. dQTcF was a dependent variable and treatment, time point, and treatment by time point interaction as the independent variables with baseline QTcF as a covariate and time-matched concentrations of moxidectin as a covariate with random effects of intercept and slope for each subject.Concentrations of zero were used for placebo.
Type of Statistical Test Other
Comments The model was used for predicting population average and 90% 2-sided bootstrapped CI of the baseline-adjusted difference between active and placebo at each time point bound at clinically relevant concentrations.
Statistical Test of Hypothesis P-Value 0.4727
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value -0.0077
Confidence Interval (2-Sided) 90%
-0.0255 to 0.0101
Estimation Comments The primary mixed effects model analysis revealed a nearly flat dQTcF - plasma concentration gradient
2.Secondary Outcome
Title Concentrations of Moxidectin in Plasma
Hide Description Concentrations of moxidectin in plasma were assessed by collection of plasma samples at pre-specified intervals after oral dosing with moxidectin. The concentration of moxidectin was determined using a validated LC MS/MS method.The pharmacokinetic time points coincided with ECG collection timepoints (within 5 minutes and no later than 10 minutes after ECG recordings). Plasma PK parameters were estimated from the concentration measurements, including maximum concentration (Cmax) for each individual and mean for each dose cohort.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic population - includes all subjects who received at least 1 dose of moxidectin and provide an adequate number of plasma samples for determination of PK parameters, analyzed according to drug received.
Arm/Group Title Moxidectin 4mg Moxidectin 8mg Moxidectin 16mg Moxidectin 24mg Moxidectin 36mg
Hide Arm/Group Description:

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

Moxidectin

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

Moxidectin

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

Moxidectin

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

Moxidectin

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

Moxidectin

Overall Number of Participants Analyzed 10 10 10 10 10
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanogram/milliliter
27.2
(30.6%)
56.7
(20.8%)
133
(27.1%)
176
(18.7%)
247
(19.7%)
3.Other Pre-specified Outcome
Title Subjects With Categorical Changes From Baseline in 12-lead Electrocardiograms (ECGs)
Hide Description Changes from baseline in QTcF exceeding regulatory standard categorical limits (> 30msec change or exceeding 450msec). Report applies to changes of 30msec - </= 60msec only
Time Frame At Baseline and Days 1, 2, 3, 4, 22 and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population - all who received at least one dose of study drug
Arm/Group Title Moxidectin 4mg Moxidectin 8mg Moxidectin 16mg Moxidectin 24mg Moxidectin 36mg Placebo
Hide Arm/Group Description:

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

Moxidectin

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

Moxidectin

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

Moxidectin

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

Moxidectin

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

Moxidectin

10 subjects will receive a single oral dose of placebo

Placebo

Overall Number of Participants Analyzed 10 10 10 10 10 10
Measure Type: Number
Unit of Measure: participants
1 0 0 0 1 1
4.Other Pre-specified Outcome
Title Change From Baseline in Heart Rate (HR) and Duration of Other Interval Parameters (PR and QRS)
Hide Description Changes from Baseline were assessed at each timepoint up to 72 hours post dose. Mean changes across the 72 hour assessment period for each parameter were calculated for each moxidectin group and the placebo group and for the population overall.
Time Frame Baseline (pre-dose) and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 60, and 72 hours post dosing
Hide Outcome Measure Data
Hide Analysis Population Description
ECG population - all subjects who receive one dose of study drug and have at least one pair of pre-dose and post-dose QTc data, analyzed as randomized
Arm/Group Title Moxidectin 4mg Moxidectin 8mg Moxidectin 16mg Moxidectin 24mg Moxidectin 36mg Placebo All Subjects
Hide Arm/Group Description:

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

Moxidectin

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

Moxidectin

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

Moxidectin

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

Moxidectin

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

Moxidectin

10 subjects will receive a single oral dose of placebo

Placebo

50 subjects received a single dose of moxidectin between 4mg and 36mg and 10 subjects received placebo
Overall Number of Participants Analyzed 10 10 10 10 10 10 60
Mean (95% Confidence Interval)
Unit of Measure: milliseconds
Change in Heart rate (HR)
-1.0
(-4.80 to 2.76)
0.5
(-2.79 to 3.85)
-1.1
(-6.35 to 4.07)
-3.6
(-10.93 to 3.65)
-1.5
(-7.34 to 4.42)
-2.9
(-6.21 to 0.39)
-0.005
(-0.018 to 0.009)
Change in PR interval
2.2
(-0.49 to 4.87)
-0.1
(-5.84 to 5.66)
-2.1
(-7.63 to 3.47)
4.6
(-3.10 to 12.34)
-3.5
(-8.86 to 1.92)
-1.8
(-5.64 to 1.98)
-0.002
(-0.016 to 0.012)
Change in QRS interval
-1.6
(-3.26 to 0.10)
-0.7
(-5.38 to 3.94)
0.4
(-1.75 to 2.49)
-0.8
(-3.55 to 2.03)
0.4
(-2.00 to 2.86)
1.2
(-0.29 to 2.59)
0.004
(-0.003 to 0.012)
Time Frame Adverse events were collected over the full 12 weeks of study follow-up
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Moxidectin 4mg Moxidectin 8mg Moxidectin 16mg Moxidectin 24mg Moxidectin 36mg Placebo
Hide Arm/Group Description

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

Moxidectin

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

Moxidectin

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

Moxidectin

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

Moxidectin

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

Moxidectin

10 subjects will receive a single oral dose of placebo

Placebo

All-Cause Mortality
Moxidectin 4mg Moxidectin 8mg Moxidectin 16mg Moxidectin 24mg Moxidectin 36mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/10 (0.00%)      0/10 (0.00%)      0/10 (0.00%)      0/10 (0.00%)      0/10 (0.00%)      0/10 (0.00%)    
Hide Serious Adverse Events
Moxidectin 4mg Moxidectin 8mg Moxidectin 16mg Moxidectin 24mg Moxidectin 36mg Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/10 (0.00%)      0/10 (0.00%)      0/10 (0.00%)      0/10 (0.00%)      0/10 (0.00%)      0/10 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Moxidectin 4mg Moxidectin 8mg Moxidectin 16mg Moxidectin 24mg Moxidectin 36mg Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/10 (30.00%)      3/10 (30.00%)      1/10 (10.00%)      0/10 (0.00%)      3/10 (30.00%)      1/10 (10.00%)    
Eye disorders             
Eye irritation  1  0/10 (0.00%)  0 1/10 (10.00%)  1 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0
Gastrointestinal disorders             
Diarrhoea  1  1/10 (10.00%)  1 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0
Abdominal discomfort  1  0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 1/10 (10.00%)  1
General disorders             
Medical device site reaction  1  1/10 (10.00%)  1 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0
Investigations             
AST increased  1  0/10 (0.00%)  0 0/10 (0.00%)  0 1/10 (10.00%)  1 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0
Blood bilirubin increased  1  0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 1/10 (10.00%)  1 0/10 (0.00%)  0
Blood cholesterol increased  1  1/10 (10.00%)  1 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0
Musculoskeletal and connective tissue disorders             
Arthralgia  1  1/10 (10.00%)  1 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0
Neck pain  1  0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 1/10 (10.00%)  1 0/10 (0.00%)  0
Pain in extremity  1  0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 1/10 (10.00%)  1 0/10 (0.00%)  0
Nervous system disorders             
Dizziness  1  0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 1/10 (10.00%)  1
Headache  1  0/10 (0.00%)  0 1/10 (10.00%)  1 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0
Respiratory, thoracic and mediastinal disorders             
Nasal congestion  1  0/10 (0.00%)  0 1/10 (10.00%)  1 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0
Oropharyngeal pain  1  0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 0/10 (0.00%)  0 1/10 (10.00%)  1 0/10 (0.00%)  0
1
Term from vocabulary, MedDRA (19.1)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Sally Kinrade, Vice President (Clinical Development)
Organization: Medicines Development Limited
Phone: +613 9629 6111
EMail: sally.kinrade@medicinesdevelopment.com
Layout table for additonal information
Responsible Party: Medicines Development for Global Health
ClinicalTrials.gov Identifier: NCT03012828    
Other Study ID Numbers: MDGH-MOX-1008
First Submitted: August 23, 2016
First Posted: January 6, 2017
Results First Submitted: December 17, 2017
Results First Posted: March 14, 2019
Last Update Posted: March 14, 2019