Tuberculosis InfectionPhase 1NCT05443178
Safety and Tolerability of Chlorquine in Addition to Anti-tuberculosis Therapy
A Phase 1 study testing Nivaquine ® (Chloroquine) in people with Tuberculosis Infection, run by University of Zurich at 1 site in Switzerland.
Trial summary
In vitro and in vivo data show promising results of adjunctive use of Chloroquine to standard tuberculosis therapy as Chloroquine enhances animicrobial effectiveness against intracellular MTB. To date, no safety data of the concurrent use of both treatments is availble. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Tuberculosis Infection
- What is being tested?
- Nivaquine ® (Chloroquine)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteSwitzerland
- Study dates
- 4 Jan 2022to 1 Jun 2025
- Phase
- Phase 1
- 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 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Informed study-specific consent (including possible pharmacogenetic analysis) as documented by signature
- Healthy volunteers aged between 18 and 50 years of age (significantly increased risk of side effects from 50 years of age with Rimstar®)
Who cannot join
- Lack of highly effective contraception during the study treatment and for 8 months after the last dose of study treatment (until Day 254, visit 7) according to 11.4 with the following consideration for participating women:
- From Day 1 (visit 2) up to Day 30 (visit 6) hormonal contraception is insufficient due to lower concentrations of estrogen and/or gestagen during and up to 14 days after Rimstar® intake. The hormonal contraception must be supplemented with a barrier method (preferably male condom).
- From Day 30 (visit 6) up to Day 254 (visit 7) hormonal contraceptive methods can be used and are considered highly effective.
- Pregnant or lactating females
- Contraindications to the class of drugs under study, e.g. known hypersensitivity or allergy to class of drugs or the investigational product, glucose-6-phosphate dehydrogenase insufficiency (favism)
- Regular treatment with drugs in the last 14 days prior to first intake of study drug (except for Paracetamol and Vitamin B6 (pyridoxine), see 8.7).
Show all 16Show fewer
- History of or concurrent, clinically significant cardiac, immunological, pulmonary, neurological, renal, gastrointestinal, dermatological, endocrinological or other major disease as determined by the Investigator and/or his representative
- History of or presence of any clinically significant abnormality in vital signs, ECG, or laboratory test results or has any medical or psychiatric condition that, in the opinion of the Investigator, may interfere with the study procedures or compromise subject safety
- History of or currently present retinopathy or other disturbances of the field of vision or the retina according to the Investigator
- History of alcohol or substance abuse for the last 3 months prior to Screening, as determined by the Investigator
- Weight less than 55kg
- Intake of grapefruit juice or grapefruits within 2 weeks before the first study drug administration and during treatment phase
- Donation of blood or blood products within a 30-day period prior to Screening
- Current enrolment or a plan to enroll in any interventional clinical study in which an investigational treatment or approved therapy for investigational use is administered within 3 months of participation to the Clear trial.
- Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant
- The investigator, his/her family members, employees and other dependent persons
Trial locations and contacts
1 site in 1 country.
Switzerland1 site, 1 recruiting
- Recruiting
Clinical Trial Center
Zurich, 8091
Khadija M'Rabet, Dr.med., +41442551365, Khadija.MRabet-Bensalah@usz.ch
Jean Marc Hoffmann, Dr.med, +41 43 253 27 49, Jean-Marc.Hoffmann@usz.ch
About this study
Official title: Open Label, Single Center, Phase 1 Dose Escalation and Extension Trial to Evaluate Safety and Tolerability of Chlorquine as Adjuvant Drug to Standard 4-drug Anti-tuberculosis Therapy in Healthy Volunteers
In vitro and in vivo data show promising results of adjunctive use of Chloroquine to standard tuberculosis therapy as Chloroquine enhances animicrobial effectiveness against intracellular MTB. To date, no safety data of the concurrent use of both treatments is availble. In a phase I trial, the investigators aim to evaluate safety and tolerability of the concurrent use of Chloroquine and standard anti-TB drug in healthy volunteers.
Read the detailed description
Even though tuberculosis (TB) remains one of the top 10 causes of death worldwide in 2019, there exists a gap in development of new diagnostics and treatments. There is a substantial need for new TB regimens, which would ideally be shorter, more tolerable and more efficient in eradicating all subpopulations of mycobacterium tuberculosis (MTB). In this regard, a promising TB drug pipeline emerges through re-use of marketed non TB-drugs, re-engineering of existing anti-TB compounds and discovery of new compounds. In vitro data showed that Chloroquine (CQ) inhibits an efflux pump expressed on macrophages. Inhibition of this pump increases intracellular concentration of Isoniazid and Pyrazinamide and enhances antimicrobial effectiveness against intracellular MTB. Recently published in vivo mouse model data confirmed the positive effect of CQ combined with the standard anti-TB therapy.
In line with global attempts to enhance effectiveness and shorten TB therapy, the investigators propose to evaluate this combination in a clinical setting. The absence of clinical study data showing safety and tolerability of CQ administered with first-line anti-TB drugs in humans shows the need for the research team to conduct this study. the investigators hypothesize that additional CQ to standard 4-drug anti-TB therapy is safe and increases the efficacy against intracellular MTB, leading to a pronounced reduction of the intracellularly hiding bacteria and overall to an accelerated reduction of bacterial load. The major advantages of this new combination with CQ and the 4-drug anti-TB therapy are, that all substances are long-term approved, commercially available drugs and that effective CQ concentrations are well achievable in humans.
Primary objective of the study is to investigate the safety and tolerability of a combination of standard doses of Nivaquine® (Chloroquine) with standard doses of Rimstar® (4-drug anti-TB therapy) in healthy volunteers.
Secondary objective of the study is to assess drug concentration of the new combination (Nivaquine® and Rimstar®) in healthy volunteers over time.
- Conditions
- Tuberculosis Infection
- Being tested
- Nivaquine ® (Chloroquine)
- Keywords
- Safety and tolerability, Chloroquin as adjuvant to standard 4-drug anti-TB therapy, Healthy volunteers, Phase I trial
- Medical subject headings
- Latent Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nivaquine ® (Chloroquine)Drug
Also called Rimstar ® (Rifampicin, Isoniazid, Ethambutol, Pyrazinamid)
dose escalation and extension trial
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | 100 mg Nivaquine and 4 Tabl Rimstar peroral once daily before breakfast for 14 days Receives: Drug: Nivaquine ® (Chloroquine) |
| Cohort 2 | Experimental | 200 mg Chloroquine and 4 Tabl Rimstar peroral once daily before breakfast for 14 days Receives: Drug: Nivaquine ® (Chloroquine) |
| Cohort 3 | Experimental | 300 mg Chloroquine and 4 Tabl Rimstar peroral once daily before breakfast for 14 days Receives: Drug: Nivaquine ® (Chloroquine) |
| Dose extension group | Experimental | Dose escalation: XX mg Chloroquine (depending on results) and 4 Tabl Rimstar peroral once daily before breakfast for 14 days Receives: Drug: Nivaquine ® (Chloroquine) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Physicial examination 1.1
Heart auscultation (normal/abnormal)
Measured: day 14
Physicial examination 1.2
Heart auscultation (normal/abnormal)
Measured: day 30
Physicial examination 2.1
lung auscultation (normal, abnormal)
Measured: day 14
Physicial examination 2.2
lung auscultation (normal, abnormal)
Measured: day 30
Physicial examination 3.1
abdominal examination (normal, abnormal)
Measured: day 14
Physicial examination 3.2
abdominal examination (normal, abnormal)
Measured: day 30
Physicial examination 4.1
lymph node palpation (normal, abnormal)
Measured: day 14
Physicial examination 4.2
lymph node palpation (normal, abnormal)
Measured: day 30
Physicial examination 5.1
reflex testing (normal, abnormal)
Measured: day 14
Physicial examination 5.2
reflex testing (normal, abnormal)
Measured: day 30
Physicial examination 6.1
test vibration sense with tuning fork (mallelor left and right X/8)
Measured: day 14
Physicial examination 6.2
test vibration sense with tuning fork (mallelor left and right X/8)
Measured: day 30
Vital Signs 1.1
heart rate (beats/min)
Measured: day 1
Vital Signs 1.2
heart rate (beats/min)
Measured: day 7
Vital Signs 1.3
heart rate (beats/min)
Measured: day 14
Vital Signs 1.4
heart rate (beats/min)
Measured: day 15
Vital Signs 1.5
heart rate (beats/min)
Measured: day 30
Vital Signs 2.1
blood pressure (mmHg)
Measured: day 1
Vital Signs 2.2
blood pressure (mmHg)
Measured: day 7
Vital Signs 2.3
blood pressure (mmHg)
Measured: day 14
Vital Signs 2.4
blood pressure (mmHg)
Measured: day 15
Vital Signs 2.5
blood pressure (mmHg)
Measured: day 30
Vital Signs 3.1
temperature (°C)
Measured: day 1
Vital Signs 3.2
temperature (°C)
Measured: day 7
Vital Signs 3.3
temperature (°C)
Measured: day 14
Vital Signs 3.4
temperature (°C)
Measured: day 15
Vital Signs 3.5
temperature (°C)
Measured: day 30
Safety Laboratory samples Panel 1.1
Sodium (mmol/l)
Measured: day 1
Safety Laboratory samples Panel 1.2
Sodium (mmol/l)
Measured: day 7
Safety Laboratory samples Panel 1.3
Sodium (mmol/l)
Measured: day 14
Safety Laboratory samples Panel 1.4
Sodium (mmol/l)
Measured: day 30
Safety Laboratory samples Panel 2.1
Potassium (mmol/l)
Measured: day 1
Safety Laboratory samples Panel 2.2
Potassium (mmol/l)
Measured: day 7
Safety Laboratory samples Panel 2.3
Potassium (mmol/l)
Measured: day 14
Safety Laboratory samples Panel 2.4
Potassium (mmol/l)
Measured: day 30
Safety Laboratory samples Panel 3.1
Calcium (mmol/l)
Measured: day 1
Safety Laboratory samples Panel 3.2
Calcium (mmol/l)
Measured: day 7
Safety Laboratory samples Panel 3.3
Calcium (mmol/l)
Measured: day 14
Safety Laboratory samples Panel 3.4
Calcium (mmol/l)
Measured: day 30
Safety Laboratory samples Panel 4.1
Creatinine (umol/l)
Measured: day 1
Safety Laboratory samples Panel 4.2
Creatinine (umol/l)
Measured: day 7
Safety Laboratory samples Panel 4.3
Creatinine (umol/l)
Measured: day 14
Safety Laboratory samples Panel 4.4
Creatinine (umol/l)
Measured: day 30
Safety Laboratory samples Panel 5.1
Total Bilirubin (umol/l)
Measured: day 1
Safety Laboratory samples Panel 5.2
Total Bilirubin (umol/l)
Measured: day 7
Safety Laboratory samples Panel 5.3
Total Bilirubin (umol/l)
Measured: day 14
Safety Laboratory samples Panel 5.4
Total Bilirubin (umol/l)
Measured: day 30
Safety Laboratory samples Panel 6.1
ALT (U/l)
Measured: day 1
Safety Laboratory samples Panel 6.2
ALT (U/l)
Measured: day 7
Safety Laboratory samples Panel 6.3
ALT (U/l)
Measured: day 14
Safety Laboratory samples Panel 6.4
ALT (U/l)
Measured: day 30
Safety Laboratory samples Panel 7.1
Glucose (mmol/l)
Measured: day 1
Safety Laboratory samples Panel 7.2
Glucose (mmol/l)
Measured: day 7
Safety Laboratory samples Panel 7.3
Glucose (mmol/l)
Measured: day 14
Safety Laboratory samples Panel 7.4
Glucose (mmol/l)
Measured: day 30
Safety Laboratory samples Panel 8.1
CRP (mg/l)
Measured: day 1
Safety Laboratory samples Panel 8.2
CRP (mg/l)
Measured: day 7
Safety Laboratory samples Panel 8.3
CRP (mg/l)
Measured: day 14
Safety Laboratory samples Panel 8.4
CRP (mg/l)
Measured: day 30
Safety Laboratory samples Panel 9.1
Haemoglobin (g/l)
Measured: day 1
Safety Laboratory samples Panel 9.2
Haemoglobin (g/l)
Measured: day 7
Safety Laboratory samples Panel 9.3
Haemoglobin (g/l)
Measured: day 14
Safety Laboratory samples Panel 9.4
Haemoglobin (g/l)
Measured: day 30
Safety Laboratory samples Panel 10.1
Platlets (G/l)
Measured: day 1
Safety Laboratory samples Panel 10.2
Platlets (G/l)
Measured: day 7
Safety Laboratory samples Panel 10.3
Platlets (G/l)
Measured: day 14
Safety Laboratory samples Panel 10.4
Platlets (G/l)
Measured: day 30
Safety Laboratory samples Panel 11.1
White blood cell (G/l)
Measured: day 1
Safety Laboratory samples Panel 11.2
White blood cell (G/l)
Measured: day 7
Safety Laboratory samples Panel 11.3
White blood cell (G/l)
Measured: day 14
Safety Laboratory samples Panel 11.4
White blood cell (G/l)
Measured: day 30
Safety Laboratory samples Panel 12.1
Blood pregnancy test (Blood beta-hCG)
Measured: day 7
Safety Laboratory samples Panel 12.2
Blood pregnancy test (Blood beta-hCG)
Measured: day 30
Urinanalysis 1.1
Dipstick: protein negative/+/++/+++
Measured: day 1
Urinanalysis 1.2
Dipstick: protein negative/+/++/+++
Measured: day 7
Urinanalysis 1.3
Dipstick: protein negative/+/++/+++
Measured: day 14
Urinanalysis 1.4
Dipstick: protein negative/+/++/+++
Measured: day 30
Urinanalysis 2.1
Dipstick: white blood cells negative/+/++/+++
Measured: day 1
Urinanalysis 2.2
Dipstick: white blood cells negative/+/++/+++
Measured: day 7
Urinanalysis 2.3
Dipstick: white blood cells negative/+/++/+++
Measured: day 14
Urinanalysis 2.4
Dipstick: white blood cells negative/+/++/+++
Measured: day 30
Urinanalysis 3.1
Dipstick: red blood cells negative/+/++/+++
Measured: day 1
Urinanalysis 3.2
Dipstick: red blood cells negative/+/++/+++
Measured: day 7
Urinanalysis 3.3
Dipstick: red blood cells negative/+/++/+++
Measured: day 14
Urinanalysis 3.4
Dipstick: red blood cells negative/+/++/+++
Measured: day 30
Urinanalysis 4.1
Dipstick: Glucose negative/+/++/+++
Measured: day 1
Urinanalysis 4.2
Dipstick: Glucose negative/+/++/+++
Measured: day 7
Urinanalysis 4.3
Dipstick: Glucose negative/+/++/+++
Measured: day 14
Urinanalysis 4.4
Dipstick: Glucose negative/+/++/+++
Measured: day 30
Safety 12 lead ECG 1.1
Rate/min
Measured: day 7
Safety 12 lead ECG 1.2
Rate/min
Measured: 30
Safety 12 lead ECG 2.1
Rhythm (regular/irregular)
Measured: day 7
Safety 12 lead ECG 2.2
Rhythm (regular/irregular)
Measured: day 30
Safety 12 lead ECG 3.1
PQ interval (ms)
Measured: day 7
Safety 12 lead ECG 3.3
PQ interval (ms)
Measured: day 30
Safety 12 lead ECG 4.1
QRS interval (ms)
Measured: day 7
Safety 12 lead ECG 4.2
QRS interval (ms)
Measured: day 30
Safety 12 lead ECG 5.1
ST Segment (normal/elevation/depression)
Measured: day 7
Safety 12 lead ECG 5.2
ST Segment (normal/elevation/depression)
Measured: day 30
Safety ophtalmological examination 1.1
Slit lamp examaniation both sides (normal/abnormal)
Measured: day 30
Safety ophtalmological examination 1.2
Refraction both sides (+/-)
Measured: day 30
Safety ophtalmological examination 1.3
Biomicroscopy of the central fundus both sides(normal/abnormal)
Measured: day 30
Safety ophtalmological examination 1.4
Applanation tonometry and stereoscopic papilla evaluation bilateral (normal/abnormal), Color sense test according to Panel D-15 right and left side (normal/abnormal)
Measured: day 30
Safety ophtalmological examination 1.5
Color sense test according to Panel D-15 bilateral (normal/abnormal)
Measured: day 30
Occurence of adverse events and serious adverse events 1.1
according to GCP Guideline
Measured: day 1
Occurence of adverse events and serious adverse events 1.2
according to GCP Guideline
Measured: day 7
Occurence of adverse events and serious adverse events 1.3
according to GCP Guideline
Measured: day 14
Occurence of adverse events and serious adverse events 1.4
according to GCP Guideline
Measured: day 15
Occurence of adverse events and serious adverse events 1.5
according to GCP Guideline
Measured: day 30
Occurence of adverse events and serious adverse events 1.6
according to GCP Guideline
Measured: day 256
Secondary outcomes (1)
Drug concentration over time measured by the pharmacokinetics
drug concentration (mg/l) of Rifampicin, Isoniazid, 25-O-Desacetylrifampicin, Ethambutol, Pyrazinamide, Chloroquine, Desethylchloroquine
Measured: day 14 prior to dosing (-15 until -5 minutes) and 1, 2, 4, 6 and 24 hours after dosing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jul 2022
- Study start4 Jan 2022
- Primary completion4 Oct 2024 (estimated)
- Study completion1 Jun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Tuberculosis InfectionStudies of the same condition, open and under way.
- More trials run by University of ZurichThe 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- 3 subjects are planned to enter each cohort. No more than 3 subjects will receive the same dose during the dose escalation phase. 3 participants are initially enrolled into the first dose cohort (100mg daily). If there is no DLT observed at Day 30, the investigators enroll 3 additional subjects into the second dose cohort (200mg daily). The targeted maximum dose of Nivaquine® is 300mg (cohort 3). Development of DLTs in ≥ 1 subject(s) in a specific dose cohort suggests that the RP2D has been exceeded, and further dose escalation is not pursued. In this case, the preceding dose level will be assumed to be the dose level for another 7 participants in the extension part of the study. If in cohort 3, no DLT is observed, an additional 7 participants will receive 300 mg chloroquine daily in the dose extension phase.
- Masking
- None (open label)
- Enrolment
- 16 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Zurich
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Marisa Kaelin, Dr. med., Principal investigator, University of Zurich
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05443178
- Sponsor's protocol ID
- Clear TB
- Status last verified
- Jun 2024
- First submitted
- 20 Aug 2020
- Last updated
- 1 Jul 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open Label, Single Center, Phase 1 Dose Escalation and Extension Trial to Evaluate Safety and Tolerability of Chlorquine as Adjuvant Drug to Standard 4-drug Anti-tuberculosis Therapy in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT05443178
- Acronym / sponsor ID
- Clear TB
- Conditions
- Tuberculosis Infection
- Keywords
- Safety and tolerability, Chloroquin as adjuvant to standard 4-drug anti-TB therapy, Healthy volunteers, Phase I trial
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 16 participants (estimated)
- Lead sponsor
- University of ZurichUniversity, hospital or other
- Study start
- 4 Jan 2022 (actual)
- Primary completion
- 4 Oct 2024 (estimated)
- Study completion
- 1 Jun 2025 (estimated)
- First posted
- 5 Jul 2022 (actual)
- 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.
In vitro and in vivo data show promising results of adjunctive use of Chloroquine to standard tuberculosis therapy as Chloroquine enhances animicrobial effectiveness against intracellular MTB. To date, no safety data of the concurrent use of both treatments is availble. In a phase I trial, the investigators aim to evaluate safety and tolerability of the concurrent use of Chloroquine and standard anti-TB drug in healthy volunteers.
Detailed description
Even though tuberculosis (TB) remains one of the top 10 causes of death worldwide in 2019, there exists a gap in development of new diagnostics and treatments. There is a substantial need for new TB regimens, which would ideally be shorter, more tolerable and more efficient in eradicating all subpopulations of mycobacterium tuberculosis (MTB). In this regard, a promising TB drug pipeline emerges through re-use of marketed non TB-drugs, re-engineering of existing anti-TB compounds and discovery of new compounds. In vitro data showed that Chloroquine (CQ) inhibits an efflux pump expressed on macrophages. Inhibition of this pump increases intracellular concentration of Isoniazid and Pyrazinamide and enhances antimicrobial effectiveness against intracellular MTB. Recently published in vivo mouse model data confirmed the positive effect of CQ combined with the standard anti-TB therapy.
In line with global attempts to enhance effectiveness and shorten TB therapy, the investigators propose to evaluate this combination in a clinical setting. The absence of clinical study data showing safety and tolerability of CQ administered with first-line anti-TB drugs in humans shows the need for the research team to conduct this study. the investigators hypothesize that additional CQ to standard 4-drug anti-TB therapy is safe and increases the efficacy against intracellular MTB, leading to a pronounced reduction of the intracellularly hiding bacteria and overall to an accelerated reduction of bacterial load. The major advantages of this new combination with CQ and the 4-drug anti-TB therapy are, that all substances are long-term approved, commercially available drugs and that effective CQ concentrations are well achievable in humans.
Primary objective of the study is to investigate the safety and tolerability of a combination of standard doses of Nivaquine® (Chloroquine) with standard doses of Rimstar® (4-drug anti-TB therapy) in healthy volunteers.
Secondary objective of the study is to assess drug concentration of the new combination (Nivaquine® and Rimstar®) in healthy volunteers over time.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- 3 subjects are planned to enter each cohort. No more than 3 subjects will receive the same dose during the dose escalation phase. 3 participants are initially enrolled into the first dose cohort (100mg daily). If there is no DLT observed at Day 30, the investigators enroll 3 additional subjects into the second dose cohort (200mg daily). The targeted maximum dose of Nivaquine® is 300mg (cohort 3). Development of DLTs in ≥ 1 subject(s) in a specific dose cohort suggests that the RP2D has been exceeded, and further dose escalation is not pursued. In this case, the preceding dose level will be assumed to be the dose level for another 7 participants in the extension part of the study. If in cohort 3, no DLT is observed, an additional 7 participants will receive 300 mg chloroquine daily in the dose extension phase.
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: Nivaquine ® (Chloroquine)100 mg Nivaquine and 4 Tabl Rimstar peroral once daily before breakfast for 14 days |
| Cohort 2 | Experimental | Drug: Nivaquine ® (Chloroquine)200 mg Chloroquine and 4 Tabl Rimstar peroral once daily before breakfast for 14 days |
| Cohort 3 | Experimental | Drug: Nivaquine ® (Chloroquine)300 mg Chloroquine and 4 Tabl Rimstar peroral once daily before breakfast for 14 days |
| Dose extension group | Experimental | Drug: Nivaquine ® (Chloroquine)Dose escalation: XX mg Chloroquine (depending on results) and 4 Tabl Rimstar peroral once daily before breakfast for 14 days |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Informed study-specific consent (including possible pharmacogenetic analysis) as documented by signature
- Healthy volunteers aged between 18 and 50 years of age (significantly increased risk of side effects from 50 years of age with Rimstar®)
Key exclusion criteria (16 listed)
- Lack of highly effective contraception during the study treatment and for 8 months after the last dose of study treatment (until Day 254, visit 7) according to 11.4 with the following consideration for participating women:
- Pregnant or lactating females
- Contraindications to the class of drugs under study, e.g. known hypersensitivity or allergy to class of drugs or the investigational product, glucose-6-phosphate dehydrogenase insufficiency (favism)
- Regular treatment with drugs in the last 14 days prior to first intake of study drug (except for Paracetamol and Vitamin B6 (pyridoxine), see 8.7).
- History of or concurrent, clinically significant cardiac, immunological, pulmonary, neurological, renal, gastrointestinal, dermatological, endocrinological or other major disease as determined by the Investigator and/or his representative
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 |
|---|---|---|
| Nivaquine ® (Chloroquine)Also: Rimstar ® (Rifampicin, Isoniazid, Ethambutol, Pyrazinamid)dose escalation and extension trial | Drug | Cohort 1, Cohort 2, Cohort 3, Dose extension group |
Primary outcome
Physicial examination 1.1
Time frame: day 14
Heart auscultation (normal/abnormal)
Physicial examination 1.2
Time frame: day 30
Heart auscultation (normal/abnormal)
Physicial examination 2.1
Time frame: day 14
lung auscultation (normal, abnormal)
Physicial examination 2.2
Time frame: day 30
lung auscultation (normal, abnormal)
Physicial examination 3.1
Time frame: day 14
abdominal examination (normal, abnormal)
Physicial examination 3.2
Time frame: day 30
abdominal examination (normal, abnormal)
Physicial examination 4.1
Time frame: day 14
lymph node palpation (normal, abnormal)
Physicial examination 4.2
Time frame: day 30
lymph node palpation (normal, abnormal)
Physicial examination 5.1
Time frame: day 14
reflex testing (normal, abnormal)
Physicial examination 5.2
Time frame: day 30
reflex testing (normal, abnormal)
Physicial examination 6.1
Time frame: day 14
test vibration sense with tuning fork (mallelor left and right X/8)
Physicial examination 6.2
Time frame: day 30
test vibration sense with tuning fork (mallelor left and right X/8)
Vital Signs 1.1
Time frame: day 1
heart rate (beats/min)
Vital Signs 1.2
Time frame: day 7
heart rate (beats/min)
Vital Signs 1.3
Time frame: day 14
heart rate (beats/min)
Vital Signs 1.4
Time frame: day 15
heart rate (beats/min)
Vital Signs 1.5
Time frame: day 30
heart rate (beats/min)
Vital Signs 2.1
Time frame: day 1
blood pressure (mmHg)
Vital Signs 2.2
Time frame: day 7
blood pressure (mmHg)
Vital Signs 2.3
Time frame: day 14
blood pressure (mmHg)
Vital Signs 2.4
Time frame: day 15
blood pressure (mmHg)
Vital Signs 2.5
Time frame: day 30
blood pressure (mmHg)
Vital Signs 3.1
Time frame: day 1
temperature (°C)
Vital Signs 3.2
Time frame: day 7
temperature (°C)
Vital Signs 3.3
Time frame: day 14
temperature (°C)
Vital Signs 3.4
Time frame: day 15
temperature (°C)
Vital Signs 3.5
Time frame: day 30
temperature (°C)
Safety Laboratory samples Panel 1.1
Time frame: day 1
Sodium (mmol/l)
Safety Laboratory samples Panel 1.2
Time frame: day 7
Sodium (mmol/l)
Safety Laboratory samples Panel 1.3
Time frame: day 14
Sodium (mmol/l)
Safety Laboratory samples Panel 1.4
Time frame: day 30
Sodium (mmol/l)
Safety Laboratory samples Panel 2.1
Time frame: day 1
Potassium (mmol/l)
Safety Laboratory samples Panel 2.2
Time frame: day 7
Potassium (mmol/l)
Safety Laboratory samples Panel 2.3
Time frame: day 14
Potassium (mmol/l)
Safety Laboratory samples Panel 2.4
Time frame: day 30
Potassium (mmol/l)
Safety Laboratory samples Panel 3.1
Time frame: day 1
Calcium (mmol/l)
Safety Laboratory samples Panel 3.2
Time frame: day 7
Calcium (mmol/l)
Safety Laboratory samples Panel 3.3
Time frame: day 14
Calcium (mmol/l)
Safety Laboratory samples Panel 3.4
Time frame: day 30
Calcium (mmol/l)
Safety Laboratory samples Panel 4.1
Time frame: day 1
Creatinine (umol/l)
Safety Laboratory samples Panel 4.2
Time frame: day 7
Creatinine (umol/l)
Safety Laboratory samples Panel 4.3
Time frame: day 14
Creatinine (umol/l)
Safety Laboratory samples Panel 4.4
Time frame: day 30
Creatinine (umol/l)
Safety Laboratory samples Panel 5.1
Time frame: day 1
Total Bilirubin (umol/l)
Safety Laboratory samples Panel 5.2
Time frame: day 7
Total Bilirubin (umol/l)
Safety Laboratory samples Panel 5.3
Time frame: day 14
Total Bilirubin (umol/l)
Safety Laboratory samples Panel 5.4
Time frame: day 30
Total Bilirubin (umol/l)
Safety Laboratory samples Panel 6.1
Time frame: day 1
ALT (U/l)
Safety Laboratory samples Panel 6.2
Time frame: day 7
ALT (U/l)
Safety Laboratory samples Panel 6.3
Time frame: day 14
ALT (U/l)
Safety Laboratory samples Panel 6.4
Time frame: day 30
ALT (U/l)
Safety Laboratory samples Panel 7.1
Time frame: day 1
Glucose (mmol/l)
Safety Laboratory samples Panel 7.2
Time frame: day 7
Glucose (mmol/l)
Safety Laboratory samples Panel 7.3
Time frame: day 14
Glucose (mmol/l)
Safety Laboratory samples Panel 7.4
Time frame: day 30
Glucose (mmol/l)
Safety Laboratory samples Panel 8.1
Time frame: day 1
CRP (mg/l)
Safety Laboratory samples Panel 8.2
Time frame: day 7
CRP (mg/l)
Safety Laboratory samples Panel 8.3
Time frame: day 14
CRP (mg/l)
Safety Laboratory samples Panel 8.4
Time frame: day 30
CRP (mg/l)
Safety Laboratory samples Panel 9.1
Time frame: day 1
Haemoglobin (g/l)
Safety Laboratory samples Panel 9.2
Time frame: day 7
Haemoglobin (g/l)
Safety Laboratory samples Panel 9.3
Time frame: day 14
Haemoglobin (g/l)
Safety Laboratory samples Panel 9.4
Time frame: day 30
Haemoglobin (g/l)
Safety Laboratory samples Panel 10.1
Time frame: day 1
Platlets (G/l)
Safety Laboratory samples Panel 10.2
Time frame: day 7
Platlets (G/l)
Safety Laboratory samples Panel 10.3
Time frame: day 14
Platlets (G/l)
Safety Laboratory samples Panel 10.4
Time frame: day 30
Platlets (G/l)
Safety Laboratory samples Panel 11.1
Time frame: day 1
White blood cell (G/l)
Safety Laboratory samples Panel 11.2
Time frame: day 7
White blood cell (G/l)
Safety Laboratory samples Panel 11.3
Time frame: day 14
White blood cell (G/l)
Safety Laboratory samples Panel 11.4
Time frame: day 30
White blood cell (G/l)
Safety Laboratory samples Panel 12.1
Time frame: day 7
Blood pregnancy test (Blood beta-hCG)
Safety Laboratory samples Panel 12.2
Time frame: day 30
Blood pregnancy test (Blood beta-hCG)
Urinanalysis 1.1
Time frame: day 1
Dipstick: protein negative/+/++/+++
Urinanalysis 1.2
Time frame: day 7
Dipstick: protein negative/+/++/+++
Urinanalysis 1.3
Time frame: day 14
Dipstick: protein negative/+/++/+++
Urinanalysis 1.4
Time frame: day 30
Dipstick: protein negative/+/++/+++
Urinanalysis 2.1
Time frame: day 1
Dipstick: white blood cells negative/+/++/+++
Urinanalysis 2.2
Time frame: day 7
Dipstick: white blood cells negative/+/++/+++
Urinanalysis 2.3
Time frame: day 14
Dipstick: white blood cells negative/+/++/+++
Urinanalysis 2.4
Time frame: day 30
Dipstick: white blood cells negative/+/++/+++
Urinanalysis 3.1
Time frame: day 1
Dipstick: red blood cells negative/+/++/+++
Urinanalysis 3.2
Time frame: day 7
Dipstick: red blood cells negative/+/++/+++
Urinanalysis 3.3
Time frame: day 14
Dipstick: red blood cells negative/+/++/+++
Urinanalysis 3.4
Time frame: day 30
Dipstick: red blood cells negative/+/++/+++
Urinanalysis 4.1
Time frame: day 1
Dipstick: Glucose negative/+/++/+++
Urinanalysis 4.2
Time frame: day 7
Dipstick: Glucose negative/+/++/+++
Urinanalysis 4.3
Time frame: day 14
Dipstick: Glucose negative/+/++/+++
Urinanalysis 4.4
Time frame: day 30
Dipstick: Glucose negative/+/++/+++
Safety 12 lead ECG 1.1
Time frame: day 7
Rate/min
Safety 12 lead ECG 1.2
Time frame: 30
Rate/min
Safety 12 lead ECG 2.1
Time frame: day 7
Rhythm (regular/irregular)
Safety 12 lead ECG 2.2
Time frame: day 30
Rhythm (regular/irregular)
Safety 12 lead ECG 3.1
Time frame: day 7
PQ interval (ms)
Safety 12 lead ECG 3.3
Time frame: day 30
PQ interval (ms)
Safety 12 lead ECG 4.1
Time frame: day 7
QRS interval (ms)
Safety 12 lead ECG 4.2
Time frame: day 30
QRS interval (ms)
Safety 12 lead ECG 5.1
Time frame: day 7
ST Segment (normal/elevation/depression)
Safety 12 lead ECG 5.2
Time frame: day 30
ST Segment (normal/elevation/depression)
Safety ophtalmological examination 1.1
Time frame: day 30
Slit lamp examaniation both sides (normal/abnormal)
Safety ophtalmological examination 1.2
Time frame: day 30
Refraction both sides (+/-)
Safety ophtalmological examination 1.3
Time frame: day 30
Biomicroscopy of the central fundus both sides(normal/abnormal)
Safety ophtalmological examination 1.4
Time frame: day 30
Applanation tonometry and stereoscopic papilla evaluation bilateral (normal/abnormal), Color sense test according to Panel D-15 right and left side (normal/abnormal)
Safety ophtalmological examination 1.5
Time frame: day 30
Color sense test according to Panel D-15 bilateral (normal/abnormal)
Occurence of adverse events and serious adverse events 1.1
Time frame: day 1
according to GCP Guideline
Occurence of adverse events and serious adverse events 1.2
Time frame: day 7
according to GCP Guideline
Occurence of adverse events and serious adverse events 1.3
Time frame: day 14
according to GCP Guideline
Occurence of adverse events and serious adverse events 1.4
Time frame: day 15
according to GCP Guideline
Occurence of adverse events and serious adverse events 1.5
Time frame: day 30
according to GCP Guideline
Occurence of adverse events and serious adverse events 1.6
Time frame: day 256
according to GCP Guideline
1 secondary outcome
Drug concentration over time measured by the pharmacokinetics
Time frame: day 14 prior to dosing (-15 until -5 minutes) and 1, 2, 4, 6 and 24 hours after dosing
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2024.
- Individual participant dataSharing planned: No
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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.
Marisa Kaelin, Dr. med. principal investigator
University of Zurich
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 Nivaquine ® (Chloroquine) in people with Tuberculosis Infection, run by University of Zurich at 1 site in Switzerland.
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 16 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: status not confirmed, as of the sponsor's last update on 1 Jul 2024. 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 Switzerland. 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 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Khadija M'Rabet, Dr. med. (+41 44 255 13 65, Khadija.MRabet-Bensalah@usz.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Physicial examination 1.1 (time frame: day 14). The study lists 110 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 1 Jul 2024.