TuberculosisPhase 4MFX468NCT01329250
Pharmacokinetics and Safety of Moxifloxacin
A Phase 4 study testing Moxifloxacin in people with Tuberculosis, run by University Medical Center Groningen at 1 site in Netherlands.
Trial summary
The main objective of this prospective clinical trial is to compare pharmacokinetics and safety and tolerability of a standard dose (400 mg) with an escalated dose (600 mg; 800 mg) of moxifloxacin (MFX). This clinical trial will provide important safety information on MFX in a higher dosage in TB patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tuberculosis
- What is being tested?
- Moxifloxacin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteNetherlands
- Study dates
- May 2011to Aug 2016
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with TB, with Mycobacterium tuberculosis (or M. africanum) by culture
- Starting treatment with MFX in a dose of 400 mg as part of their TB treatment
Who cannot join
- Contra-indication for MFX
- Baseline QTc-interval > 450 msec
- History of resuscitation
- History of ventricular tachycardia (including Torsades de Pointes)
- Family history of sudden cardiac death or Torsades de Pointes
- Additional risk factors for Torsades de Pointes (including known heart failure, Left ventricular hypertrophy)
Show all 12Show fewer
- Use of concomitant treatment with QT/QTc prolonging drugs (including anti-dysrhythmics class IA and III, antipsychotics, tricyclic antidepressants or the antihistaminic drug terfenadine)
- Abnormal electrolytes (K, Mg, Na, Ca)
- Abnormal cardiac repolarisation on screening/baseline ECG
- History of adverse events to fluoroquinolones
- HIV co-infection
- RIF treatment during last 3 weeks before start of the study. After a washout period of 3 weeks the patient can be included.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Pharmacokinetics and Safety of Moxifloxacin; a Dose Escalation in Patients With Tuberculosis
The main objective of this prospective clinical trial is to compare pharmacokinetics and safety and tolerability of a standard dose (400 mg) with an escalated dose (600 mg; 800 mg) of moxifloxacin (MFX). This clinical trial will provide important safety information on MFX in a higher dosage in TB patients.
Read the detailed description
Moxifloxacin (MFX) is a fluoroquinolone with a high in vitro and in vivo bactericidal activity against Mycobacterium tuberculosis. A daily dose of 600-800 mg MFX should be considered for optimal killing of the involved mycobacteria and suppression of drug resistance, which is higher than the currently used dose of 400 mg once daily. In general, safety data to support switching to the suggested higher dose are limited.
For this purpose, twenty tuberculosis patients will start on a standard dose of MFX 400 mg once daily. After 8 days the dose will be increased to 600 mg once daily and on the 15th day of treatment, the dose of MFX will be escalated to 800 mg. In patients who have been treated with rifampicin (RIF) in the past three weeks prior to start of MFX treatment an additional washout period of 3 weeks to reduce the rifampicin induced enzymatic activity will precede the dose escalation.
- Conditions
- Tuberculosis
- Being tested
- Moxifloxacin
- Keywords
- Tuberculosis, Moxifloxacin, Pharmacokinetics, Safety
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MoxifloxacinDrug
Also called MFX
Patients will start on a standard dose of MFX 400 mg once daily. After 8 days the dose will be increased to 600 mg once daily and on the 15th day of treatment, the dose of MFX will be escalated to 800 mg. In patients who have been treated with rifampicin (RIF) in the past three weeks prior to start of MFX treatment an additional washout period of 3 weeks to reduce the rifampicin induced enzymatic activity will precede the dose escalation.
| Study group | Role | What they receive |
|---|---|---|
| Moxifloxacin | Experimental | Moxifloxacinin escalating dose Receives: Drug: Moxifloxacin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Bound area under the plasma concentration-time curve (AUC0-24h) relative to the minimal inhibitory concentration (MIC)
% of patients who will reach an AUC0-24h/MIC ratio of at least 100 after administration of 400 mg (i.e. 7 days post dosage) moxifloxacin
Measured: 7 days post dosage
Unbound AUC0-24h/MIC ratio as predictive parameter for efficacy of unbound MFX dose escalated treatment of tuberculosis
% of patients who will reach an unbound AUC0-24h/MIC ratio of at least 60 after administration of 400 mg (i.e. 7 day post dosage) moxifloxacin.
Measured: 7 days post dosage
Bound AUC0-24h/Mutant Prevention Concentration (MPC) ratio
% of patients who will reach an adequate AUC0-24h/MPC ratio of at least 93 after administration of 400 mg (i.e. 7 days post dosage) moxifloxacin
Measured: 7 days post dosage
Unbound AUC0-24h/MPC ratio as predictive parameter for efficacy of unbound MFX dose escalated treatment of tuberculosis and suppression of MFX resistance
% of patients who will reach an unbound AUC0-24h/MPC ratio of at least 53 after administration of 400 mg (i.e. 7 days post dosage) moxifloxacin
Measured: 7 days post dosage
% of patients having adverse effects, including QT interval prolongation, hypersensitive reactions, diarrhoea, vomiting and hepatic or renal injury
- QT interval in msec
- Percentage of patients developing hepatic toxicity grade ≥ 2 or 3 Common Toxicity Criteria (CTC)
- Percentage of patients developing renal toxicity grade ≥ 2 CTC
Measured: up to 21 days
Bound area under the plasma concentration-time curve (AUC0-24h) relative to the minimal inhibitory concentration (MIC)
% of patients who will reach an AUC0-24h/MIC ratio of at least 100 after administration of 600 mg (i.e. 14 days post dosage) moxifloxacin
Measured: 14 days post dosage
Bound area under the plasma concentration-time curve (AUC0-24h) relative to the minimal inhibitory concentration (MIC)
% of patients who will reach an AUC0-24h/MIC ratio of at least 100 after administration of 800 mg (i.e. 21 days post dosage) moxifloxacin
Measured: 21 days post dosage
Unbound AUC0-24h/MIC ratio as predictive parameter for efficacy of unbound MFX dose escalated treatment of tuberculosis
% of patients who will reach an unbound AUC0-24h/MIC ratio of at least 60 after administration of 600 mg (i.e. 14 days post dosage) moxifloxacin.
Measured: 14 days post dosage
Unbound AUC0-24h/MIC ratio as predictive parameter for efficacy of unbound MFX dose escalated treatment of tuberculosis
% of patients who will reach an unbound AUC0-24h/MIC ratio of at least 60 after administration of 800 mg (21 days post dosage) moxifloxacin.
Measured: 21 days post dosage
Bound AUC0-24h/Mutant Prevention Concentration (MPC) ratio
% of patients who will reach an adequate AUC0-24h/MPC ratio of at least 93 after administration of 600 mg (i.e. 14 days post dosage) moxifloxacin
Measured: 14 post dosage
Bound AUC0-24h/Mutant Prevention Concentration (MPC) ratio
% of patients who will reach an adequate AUC0-24h/MPC ratio of at least 93 after administration of 800 mg (i.e. 21 days post dosage) moxifloxacin
Measured: 21 post dosage
Unbound AUC0-24h/MPC ratio as predictive parameter for efficacy of unbound MFX dose escalated treatment of tuberculosis and suppression of MFX resistance
% of patients who will reach an unbound AUC0-24h/MPC ratio of at least 53 after administration of 600 mg (i.e. 14 days post dosage) and moxifloxacin
Measured: 14 days post dosage
Unbound AUC0-24h/MPC ratio as predictive parameter for efficacy of unbound MFX dose escalated treatment of tuberculosis and suppression of MFX resistance
% of patients who will reach an unbound AUC0-24h/MPC ratio of at least 53 after administration of 800 mg (i.e. 21 days post dosage) moxifloxacin
Measured: 21 days post dosage
Secondary outcomes (8)
Evaluation of the predictive performance of the limited sampling strategies based on a pharmacokinetic population model to calculate AUC0-24h. Several limited sampling points will be evaluated.
Several limited sampling strategies to predict moxifloxacin AUC0-24h, based on limited sampling points, will be evaluated after administration of 400 mg (i.e. 7 days post dosage)moxifloxacin
Measured: 7 days post dosage
Correlation between MFX concentration (mg/L) and QT interval (msec)
Correlation between MFX concentration (mg/L) and QT interval (msec) after administration of 400 mg (i.e. 7 days post dosage) moxifloxacin
Measured: 7 days post dosage
Correlation of drug exposure (AUC) and adverse effects
- vomiting and diarrhoea
- QT interval (msec)
Measured: up to 21 days
Correlation between the genetic risk score and MFX induced QT prolongation
Measured: up to 21 days
Evaluation of the predictive performance of the limited sampling strategies based on a pharmacokinetic population model to calculate AUC0-24h. Several limited sampling points will be evaluated.
Several limited sampling strategies to predict moxifloxacin AUC0-24h, based on limited sampling points, will be evaluated after administration of 600 mg (i.e. 14 days post dosage) moxifloxacin
Measured: 14 days post dosage
Evaluation of the predictive performance of the limited sampling strategies based on a pharmacokinetic population model to calculate AUC0-24h. Several limited sampling points will be evaluated.
Several limited sampling strategies to predict moxifloxacin AUC0-24h, based on limited sampling points, will be evaluated after administration of 800 mg (i.e. 21 days post dosage) moxifloxacin
Measured: 21 days post dosage
Correlation between MFX concentration (mg/L) and QT interval (msec)
Correlation between MFX concentration (mg/L) and QT interval (msec) after administration of 600 mg (i.e. 14 days post dosage) moxifloxacin
Measured: 14 days post dosage
Correlation between MFX concentration (mg/L) and QT interval (msec)
Correlation between MFX concentration (mg/L) and QT interval (msec) after administration of 800 mg (i.e. 21 days post dosage) moxifloxacin
Measured: 21 days post dosage
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2011 (estimated)
- Study startMay 2011
- Primary completionJun 2015
- Study completionAug 2016
Why it stopped: slow enrolment of patients and new insights
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- More trials run by University Medical Center GroningenThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Medical Center Groningen
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, JWC Alffenaar, University Medical Center Groningen
- Investigators
- Jos GW Kosterink, PharmD, PhD, Study chair, Univeristy Medical Center GroningenJan-Willem C Alffenaar, PharmD, PhD, Principal investigator, University Medical Center Groningen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01329250
- Sponsor's protocol ID
- MFX468
- Acronym
- MFX468
- Status last verified
- Nov 2016
- First submitted
- 8 Mar 2011
- Last updated
- 18 Nov 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics and Safety of Moxifloxacin; a Dose Escalation in Patients With Tuberculosis
- ClinicalTrials.gov ID
- NCT01329250
- Acronym / sponsor ID
- MFX468 / MFX468
- Conditions
- Tuberculosis
- Keywords
- Tuberculosis, Moxifloxacin, Pharmacokinetics, Safety
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: slow enrolment of patients and new insights
- Enrolment
- 9 participants (actual)
- Lead sponsor
- University Medical Center GroningenUniversity, hospital or other
- Study start
- May 2011
- Primary completion
- Jun 2015 (actual)
- Study completion
- Aug 2016 (actual)
- First posted
- 5 Apr 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main objective of this prospective clinical trial is to compare pharmacokinetics and safety and tolerability of a standard dose (400 mg) with an escalated dose (600 mg; 800 mg) of moxifloxacin (MFX). This clinical trial will provide important safety information on MFX in a higher dosage in TB patients.
Detailed description
Moxifloxacin (MFX) is a fluoroquinolone with a high in vitro and in vivo bactericidal activity against Mycobacterium tuberculosis. A daily dose of 600-800 mg MFX should be considered for optimal killing of the involved mycobacteria and suppression of drug resistance, which is higher than the currently used dose of 400 mg once daily. In general, safety data to support switching to the suggested higher dose are limited.
For this purpose, twenty tuberculosis patients will start on a standard dose of MFX 400 mg once daily. After 8 days the dose will be increased to 600 mg once daily and on the 15th day of treatment, the dose of MFX will be escalated to 800 mg. In patients who have been treated with rifampicin (RIF) in the past three weeks prior to start of MFX treatment an additional washout period of 3 weeks to reduce the rifampicin induced enzymatic activity will precede the dose escalation.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Moxifloxacin | Experimental | Drug: MoxifloxacinMoxifloxacinin escalating dose |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patients with TB, with Mycobacterium tuberculosis (or M. africanum) by culture
- Starting treatment with MFX in a dose of 400 mg as part of their TB treatment
Key exclusion criteria (12 listed)
- Contra-indication for MFX
- Baseline QTc-interval > 450 msec
- History of resuscitation
- History of ventricular tachycardia (including Torsades de Pointes)
- Family history of sudden cardiac death or Torsades de Pointes
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 |
|---|---|---|
| MoxifloxacinAlso: MFXPatients will start on a standard dose of MFX 400 mg once daily. After 8 days the dose will be increased to 600 mg once daily and on the 15th day of treatment, the dose of MFX will be escalated to 800 mg. In patients who have been treated with rifampicin (RIF) in the past three weeks prior to start of MFX treatment an additional washout period of 3 weeks to reduce the rifampicin induced enzymatic activity will precede the dose escalation. | Drug | Moxifloxacin |
Primary outcome
Bound area under the plasma concentration-time curve (AUC0-24h) relative to the minimal inhibitory concentration (MIC)
Time frame: 7 days post dosage
% of patients who will reach an AUC0-24h/MIC ratio of at least 100 after administration of 400 mg (i.e. 7 days post dosage) moxifloxacin
Unbound AUC0-24h/MIC ratio as predictive parameter for efficacy of unbound MFX dose escalated treatment of tuberculosis
Time frame: 7 days post dosage
% of patients who will reach an unbound AUC0-24h/MIC ratio of at least 60 after administration of 400 mg (i.e. 7 day post dosage) moxifloxacin.
Bound AUC0-24h/Mutant Prevention Concentration (MPC) ratio
Time frame: 7 days post dosage
% of patients who will reach an adequate AUC0-24h/MPC ratio of at least 93 after administration of 400 mg (i.e. 7 days post dosage) moxifloxacin
Unbound AUC0-24h/MPC ratio as predictive parameter for efficacy of unbound MFX dose escalated treatment of tuberculosis and suppression of MFX resistance
Time frame: 7 days post dosage
% of patients who will reach an unbound AUC0-24h/MPC ratio of at least 53 after administration of 400 mg (i.e. 7 days post dosage) moxifloxacin
% of patients having adverse effects, including QT interval prolongation, hypersensitive reactions, diarrhoea, vomiting and hepatic or renal injury
Time frame: up to 21 days
* QT interval in msec * Percentage of patients developing hepatic toxicity grade ≥ 2 or 3 Common Toxicity Criteria (CTC) * Percentage of patients developing renal toxicity grade ≥ 2 CTC
Bound area under the plasma concentration-time curve (AUC0-24h) relative to the minimal inhibitory concentration (MIC)
Time frame: 14 days post dosage
% of patients who will reach an AUC0-24h/MIC ratio of at least 100 after administration of 600 mg (i.e. 14 days post dosage) moxifloxacin
Bound area under the plasma concentration-time curve (AUC0-24h) relative to the minimal inhibitory concentration (MIC)
Time frame: 21 days post dosage
% of patients who will reach an AUC0-24h/MIC ratio of at least 100 after administration of 800 mg (i.e. 21 days post dosage) moxifloxacin
Unbound AUC0-24h/MIC ratio as predictive parameter for efficacy of unbound MFX dose escalated treatment of tuberculosis
Time frame: 14 days post dosage
% of patients who will reach an unbound AUC0-24h/MIC ratio of at least 60 after administration of 600 mg (i.e. 14 days post dosage) moxifloxacin.
Unbound AUC0-24h/MIC ratio as predictive parameter for efficacy of unbound MFX dose escalated treatment of tuberculosis
Time frame: 21 days post dosage
% of patients who will reach an unbound AUC0-24h/MIC ratio of at least 60 after administration of 800 mg (21 days post dosage) moxifloxacin.
Bound AUC0-24h/Mutant Prevention Concentration (MPC) ratio
Time frame: 14 post dosage
% of patients who will reach an adequate AUC0-24h/MPC ratio of at least 93 after administration of 600 mg (i.e. 14 days post dosage) moxifloxacin
Bound AUC0-24h/Mutant Prevention Concentration (MPC) ratio
Time frame: 21 post dosage
% of patients who will reach an adequate AUC0-24h/MPC ratio of at least 93 after administration of 800 mg (i.e. 21 days post dosage) moxifloxacin
Unbound AUC0-24h/MPC ratio as predictive parameter for efficacy of unbound MFX dose escalated treatment of tuberculosis and suppression of MFX resistance
Time frame: 14 days post dosage
% of patients who will reach an unbound AUC0-24h/MPC ratio of at least 53 after administration of 600 mg (i.e. 14 days post dosage) and moxifloxacin
Unbound AUC0-24h/MPC ratio as predictive parameter for efficacy of unbound MFX dose escalated treatment of tuberculosis and suppression of MFX resistance
Time frame: 21 days post dosage
% of patients who will reach an unbound AUC0-24h/MPC ratio of at least 53 after administration of 800 mg (i.e. 21 days post dosage) moxifloxacin
8 secondary outcomes
Evaluation of the predictive performance of the limited sampling strategies based on a pharmacokinetic population model to calculate AUC0-24h. Several limited sampling points will be evaluated.
Time frame: 7 days post dosage
Correlation between MFX concentration (mg/L) and QT interval (msec)
Time frame: 7 days post dosage
Correlation of drug exposure (AUC) and adverse effects
Time frame: up to 21 days
Correlation between the genetic risk score and MFX induced QT prolongation
Time frame: up to 21 days
Evaluation of the predictive performance of the limited sampling strategies based on a pharmacokinetic population model to calculate AUC0-24h. Several limited sampling points will be evaluated.
Time frame: 14 days post dosage
Evaluation of the predictive performance of the limited sampling strategies based on a pharmacokinetic population model to calculate AUC0-24h. Several limited sampling points will be evaluated.
Time frame: 21 days post dosage
Correlation between MFX concentration (mg/L) and QT interval (msec)
Time frame: 14 days post dosage
Correlation between MFX concentration (mg/L) and QT interval (msec)
Time frame: 21 days post dosage
Results and safety
The study was stopped early (reason given: slow enrolment of patients and new insights). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2016.
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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.
Jos GW Kosterink, PharmD, PhD study chair
Univeristy Medical Center Groningen
Jan-Willem C Alffenaar, PharmD, PhD principal investigator
University Medical Center Groningen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Moxifloxacin in people with Tuberculosis, run by University Medical Center Groningen at 1 site in Netherlands.
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 2 inclusion and 12 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: stopped early, as of the sponsor's last update on 18 Nov 2016. 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 Netherlands. 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: slow enrolment of patients and new insights). Results are not available in the source record.
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?
Bound area under the plasma concentration-time curve (AUC0-24h) relative to the minimal inhibitory concentration (MIC) (time frame: 7 days post dosage). The study lists 13 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 Nov 2016.