QT Effects in Healthy VolunteersPhase 1NCT03012828
Effect of a Single Oral Dose of Moxidectin on the Cardiac QT Interval of Healthy Volunteers
A Phase 1 study testing Moxidectin in people with QT Effects in Healthy Volunteers, run by Medicines Development for Global Health at 1 site in United States.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 to 50 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- QT Effects in Healthy Volunteers
- What is being tested?
- Moxidectin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2017to May 2017
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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;
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- 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);
- Current use or has used tobacco- or nicotine-containing products (eg, cigarettes, cigars, chewing tobacco, snuff, etc.) within 14 days before study drug dosing;
- Blood donation or significant blood loss within 30 days before Check-in (Day -1) or donated plasma within 7 days before Check-in (Day -1);
- Presence of hepatitis B surface antigen or antibodies to human immunodeficiency virus (HIV) or hepatitis C virus at Screening;
- Poor venous access in both arms;
- Unable to understand verbal or written English or any other language for which a certified translation of the informed consent form is available;
- For any reason, is deemed by the investigator or medically qualified designee to be inappropriate for this study, including a subject who is unable to communicate or cooperate with the investigator, and/or is unwilling to comply with protocol defined procedures and complete the study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Potential Effect of a Single Oral Dose of Moxidectin on the Cardiac QT Interval of Healthy Volunteers
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
Read the detailed description
Moxidectin is being developed as a treatment for Onchocerciasis (river blindness), a serious, debilitating, disease caused by a parasitic worm, Onchocerca volvulus.
Five dose levels of moxidectin will be administered to healthy volunteers and ECG assessments undertaken at pre-specified pharmacokinetic time points to correlate QT interval with moxidectin concentration in plasma.
- Conditions
- QT Effects in Healthy Volunteers
- Being tested
- Moxidectin, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MoxidectinDrug
Moxidectin is a broad spectrum macrocyclic lactone endectocide
PlaceboOther
| Study group | Role | What they receive |
|---|---|---|
| Moxidectin 4mg | Experimental | 10 subjects will receive a single oral dose of moxidectin 4mg Receives: Drug: Moxidectin |
| Moxidectin 8mg | Experimental | 10 subjects will receive a single oral dose of moxidectin 8mg Receives: Drug: Moxidectin |
| Moxidectin 16mg | Experimental | 10 subjects will receive a single oral dose of moxidectin 16mg Receives: Drug: Moxidectin |
| Moxidectin 24mg | Experimental | 10 subjects will receive a single oral dose of moxidectin 24mg Receives: Drug: Moxidectin |
| Moxidectin 36mg | Experimental | 10 subjects will receive a single oral dose of moxidectin 36mg Receives: Drug: Moxidectin |
| Placebo | Placebo comparator | 10 subjects will receive a single oral dose of placebo Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2017 (estimated)
- Study startJan 2017
- Primary completionMar 2017
- Study completionMay 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for QT Effects in Healthy VolunteersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medicines Development for Global Health
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mark Sullivan, Study director, Sponsor GmbH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03012828
- Sponsor's protocol ID
- MDGH-MOX-1008
- Status last verified
- Mar 2019
- First submitted
- 23 Aug 2016
- Last updated
- 14 Mar 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No: Healthy volunteer study: results are not useful to individuals
Publications
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.
PubMed 30117300
Study at a glance
From the registry record, last updated by the sponsor on 14 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Potential Effect of a Single Oral Dose of Moxidectin on the Cardiac QT Interval of Healthy Volunteers
- ClinicalTrials.gov ID
- NCT03012828
- Acronym / sponsor ID
- MDGH-MOX-1008
- Conditions
- QT Effects in Healthy Volunteers
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Medicines Development for Global HealthUniversity, hospital or other
- Study start
- Jan 2017
- Primary completion
- Mar 2017 (actual)
- Study completion
- May 2017 (actual)
- First posted
- 6 Jan 2017 (estimated)
- Results
- Posted 14 Mar 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
Moxidectin is being developed as a treatment for Onchocerciasis (river blindness), a serious, debilitating, disease caused by a parasitic worm, Onchocerca volvulus.
Five dose levels of moxidectin will be administered to healthy volunteers and ECG assessments undertaken at pre-specified pharmacokinetic time points to correlate QT interval with moxidectin concentration in plasma.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Moxidectin 4mg | Experimental | Drug: Moxidectin10 subjects will receive a single oral dose of moxidectin 4mg |
| Moxidectin 8mg | Experimental | Drug: Moxidectin10 subjects will receive a single oral dose of moxidectin 8mg |
| Moxidectin 16mg | Experimental | Drug: Moxidectin10 subjects will receive a single oral dose of moxidectin 16mg |
| Moxidectin 24mg | Experimental | Drug: Moxidectin10 subjects will receive a single oral dose of moxidectin 24mg |
| Moxidectin 36mg | Experimental | Drug: Moxidectin10 subjects will receive a single oral dose of moxidectin 36mg |
| Placebo | Placebo comparator | Other: Placebo10 subjects will receive a single oral dose of placebo |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (21 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MoxidectinMoxidectin is a broad spectrum macrocyclic lactone endectocide | Drug | Moxidectin 16mg, Moxidectin 24mg, Moxidectin 36mg, Moxidectin 4mg, Moxidectin 8mg |
| Placebo | Other | Placebo |
Primary outcome
Mean Change From Baseline in QTc Interval (Corrected by Friderica's Formula, dQTcF) Associated With Plasma Moxidectin Concentrations After a Single Dose
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
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.
1 secondary outcome
Concentrations of Moxidectin in Plasma
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Mar 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30117300Kinrade 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.
- Individual participant dataSharing planned: No. Healthy volunteer study: results are not useful to individuals
Related trials for QT Effects in Healthy Volunteers
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark Sullivan study director
Sponsor GmbH
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Moxidectin in people with QT Effects in Healthy Volunteers, run by Medicines Development for Global Health at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Mar 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Change From Baseline in QTc Interval (Corrected by Friderica's Formula, dQTcF) Associated With Plasma Moxidectin Concentrations After a Single Dose (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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03012828, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Mar 2019.