TuberculosisPhase 1NCT03423030
Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Ex-vivo Antitubercular Activity of PBTZ169 Formulation
A Phase 1 study testing PBTZ169 Formulation and PBTZ169 NCP in people with Tuberculosis and Tuberculosis, Pulmonary, run by Innovative Medicines for Tuberculosis at 1 site in Switzerland.
Trial summary
This is a randomized, double-blind, placebo-controlled, single ascending dose study conducted at one study center in Switzerland. Four (4) panels (A, B, C and D) of 8 male subjects (6 active and 2 placebo) each undergoing 2 investigation periods and receiving either single doses of PBTZ169 at increasing dose levels or… Read more about this study
- Who is it for?
- Ages 18 to 48 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Tuberculosis, Tuberculosis, Pulmonary
- What is being tested?
- PBTZ169 Formulation and PBTZ169 NCP
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 1 siteSwitzerland
- Study dates
- 5 Dec 2017to 28 Mar 2018
- 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 48 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy male subjects aged between 18 and 48 years
- Body weight (BW) ranging between 55 and 95 kg, providing body mass index (BMI) is between 18 and 28 kg/m2
- Absence of significant findings in the medical history and physical examination as judged by the Investigator, especially for cardiovascular, pulmonary, haematological and nervous systems
- Absence of significant laboratory abnormalities as judged by the Investigator. Gilbert's syndrome (increased total and unconjugated bilirubin when fasting) will be accepted if mild
- Absence of clinically significant abnormalities on 12-lead ECG
- Negative urine drug screen (amphetamines, benzodiazepines, cannabis, cocaine, opiates)
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- Commitment to refrain from travel outside Europe over the whole study duration
- Ability to understand the procedures, agreement to participate and willingness to give written informed consent
- Co-operative attitude and availability for scheduled visits over the entire study period
Who cannot join
- History of major cardiovascular, pulmonary, hepatic, immunological, renal, haematological, gastrointestinal, genitourinary, neurological, or rheumatologic disorders
- Active diseases of any type, including inflammatory disorders and infections. Mild acne is permissible providing no systemic or local treatment is provided or planned (except for cleaning lotions)
- History of significant allergy or asthma. Allergic rhinitis or conjunctivitis is acceptable if non-symptomatic when starting the study and if symptoms are not anticipated to occur during the study to a point that would require corticosteroid therapy (e.g. in case of annual use)
- History of cardiovascular dysfunction if considered as clinically relevant (conduction abnormality, arrhythmia, bradycardia, angina pectoris, cardiac hypertrophy unless elicited by training, pulmonary embolism)
- Hypertension defined as supine blood pressure >150/90 mmHg or recurrent hypotensive events considered as clinically relevant or documented orthostatic hypotension
- Sick sinus syndrome, known long QT syndrome, reproducible observation of QTc ≥ 440 msec or of pronounced sinus bradycardia (<40 bpm/min)
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- Intense sport activities. Moderate sport is acceptable and activities should remain fairly constant throughout the study
- Any clinically significant laboratory values on screening that are not within normal range on single repeat (Gilbert's syndrome acceptable if mild)
- Positive hepatitis B and C antigen screen
- Positive HIV antibody screen or screen not performed
- Any recent acute illness or sequelae thereof which could expose the subject to a higher risk or might confound the results of the study
- Treatment in the previous three months with any drug known to have well-defined potential for toxicity to a major organ
- History of hypersensitivity to any drug if considered as serious
- Use of any medication the week prior to study or as based on the 5 plasma half-life rule and throughout study, including aspirin or other over-the-counter (OTC) preparations. Paracetamol is permissible before and during the study as a rescue medication but only with Investigator's permission
- Participation in a clinical investigation or blood donation of 500 ml within the past 3 months
- History of relevant alcohol or drug abuse
- Usual smoking during the last month before participation in the study. Consumption of ≤ 5 cigarettes/day or equivalent is acceptable providing the subject can totally refrain from smoking from one week before and during the whole study duration
- Usual consumption of a large quantity of coffee, tea, chocolate (more than 4 cups/day) or equivalent (Cola drinks), during the last month before participation in the study
- Current regular (i.e. 3 times per week or more) consumption of large quantities of alcohol or wine (>0.5 L wine/day) or equivalent (i.e. more than 35 g ethanol per day), during the last month before participation in the study
- Project to conceive a child during the study period (by principle of precaution, while no indication exists for a definite reproductive risk following paternal exposure)
- Psychological status which could impact on the subject's ability to give informed consent
- Any feature of the subject's medical history or present condition which, in the Investigator's opinion, could confound the results of the study, complicate its interpretation, or represent a potential risk for the subject
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
Division of Clinical Pharmacology, Centre Hospitalier Universitaire Vaudois (CHUV)
Lausanne, Canton of Vaud, 1011
About this study
Official title: Safety, Tolerability, Pharmacokinetic Profile and Ex-vivo Antitubercular Activity of PBTZ169 Formulated as Spray- Dried Dispersion Versus Native Crystal Powder: Single Ascending Doses, Randomized, Placebo- Controlled, Cross-over Phase Ia Trial in Healthy Volunteers
This is a randomized, double-blind, placebo-controlled, single ascending dose study conducted at one study center in Switzerland.
Four (4) panels (A, B, C and D) of 8 male subjects (6 active and 2 placebo) each undergoing 2 investigation periods and receiving either single doses of PBTZ169 at increasing dose levels or a matching placebo.
Read more
Subjects will participate in only one panel. Blocks of 4 subjects (3 under active treatment, 1 under placebo) will be investigated in parallel. Panels A and B are interleaved.
Safety will be assessed throughout the study; serial ECGs and serial blood samples will be collected for the safety and PK assessment of PBTZ169.
Dose escalation will be allowed once the Trial Safety Board has determined that adequate safety and tolerability after panel B and panel C completion has been demonstrated to permit proceeding to the next panel.
- Conditions
- Tuberculosis, Tuberculosis, Pulmonary
- Being tested
- PBTZ169 Formulation, Placebo, PBTZ169 NCP
- Medical subject headings
- Tuberculosis, Tuberculosis, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PBTZ169 FormulationDrug
PBTZ169 Formulation supplied as powder for oral solution
PlaceboDrug
matching placebo supplied as powder for oral solution
PBTZ169 NCPDrug
PBTZ169 NCP supplied as powder for oral solution
| Study group | Role | What they receive |
|---|---|---|
| Panel A - Active | Experimental | N = 6, 10 mg then 40 mg of PBTZ169 Formulation Receives: Drug: PBTZ169 Formulation |
| Panel A - Placebo | Placebo comparator | N = 2, 10 mg then 40 mg of matching placebo Receives: Drug: Placebo |
| Panel B - Active | Experimental | N = 6, 20 mg then 80 mg of PBTZ169 Formulation Receives: Drug: PBTZ169 Formulation |
| Panel B - Placebo | Placebo comparator | N = 2, 20 mg then 80 mg of matching placebo Receives: Drug: Placebo |
| Panel C - Active | Experimental | N = 6, First dosing of Panel C with 160 mg PBTZ169 Formulation then Second dosing of Panel C with 160 mg PBTZ169 Native Crystalline Powder (NCP) Receives: Drug: PBTZ169 Formulation; Drug: PBTZ169 NCP |
| Panel C - Placebo | Active comparator | N = 2, 160 mg of matching placebo for the two interventions Receives: Drug: Placebo |
| Panel D - Active | Experimental | N = 6, First dosing of Panel D with 320 mg PBTZ169 Formulation then Second dosing of Panel D with 320 mg PBTZ169 Native Crystalline Powder (NCP) Receives: Drug: PBTZ169 Formulation; Drug: PBTZ169 NCP |
| Panel D - Placebo | Active comparator | N = 2, 320 mg of matching placebo for the two interventions Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability of increasing single oral doses of PBTZ169 Formulation in healthy male adult subjects evaluated by Treatment Emergent Adverse Events (TEAEs).
Evaluation by thorough monitoring of Treatment Emergent Adverse Events (TEAEs) following doses of PBTZ169 Formulation, PBTZ169 NCP or placebo
Measured: Days 0-17
Secondary outcomes (5)
Relative oral bioavailability assessment of the PBTZ169 Formulation in comparison to NCP in healthy male subjects
Estimation from the ratio of area under plasma concentration curves (AUCs) determined after the administration of each formulation
Measured: Days 0-2
Pharmacokinetics (PK) of single oral doses of PBTZ169 using Cmax
Determination of non-compartmental PK parameter Maximum Plasma Concentration [Cmax] after determination of the amount of the parent compound and its known metabolites in plasma samples
Measured: Days 0-2
Pharmacokinetics (PK) of single oral doses of PBTZ169 using Tmax
Determination of non-compartmental PK parameter Time of maximum observed Plasma Concentration [Tmax] after determination of the amount of the parent compound and its known metabolites in plasma samples
Measured: Days 0-2
Pharmacodynamics (PD) exploration after single oral doses of PBTZ169 Formulation and NCP
Determination of ex-vivo antitubercular activity of serum samples obtained from subjects
Measured: Days 0-1
Broncho-alveolar passage exploration after single oral doses of PBTZ169 Formulation and NCP (tentative)
PBTZ169 concentrations in sputum samples collected by hypertonic NaCl-induction
Measured: Days 0-1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2018
- Study start5 Dec 2017
- Primary completion28 Mar 2018
- Study completion28 Mar 2018
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.
- 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
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Innovative Medicines for Tuberculosis
- Sponsor type
- University, hospital or other
- Collaborators
- Bill and Melinda Gates Foundation
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03423030
- Sponsor's protocol ID
- IM-006-11
- Status last verified
- Jul 2018
- First submitted
- 24 Jan 2018
- Last updated
- 13 Jul 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety, Tolerability, Pharmacokinetic Profile and Ex-vivo Antitubercular Activity of PBTZ169 Formulated as Spray- Dried Dispersion Versus Native Crystal Powder: Single Ascending Doses, Randomized, Placebo- Controlled, Cross-over Phase Ia Trial in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT03423030
- Acronym / sponsor ID
- IM-006-11
- Conditions
- Tuberculosis, Tuberculosis, Pulmonary
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Innovative Medicines for TuberculosisUniversity, hospital or other
- Collaborators
- Bill and Melinda Gates Foundation
- Study start
- 5 Dec 2017 (actual)
- Primary completion
- 28 Mar 2018 (actual)
- Study completion
- 28 Mar 2018 (actual)
- First posted
- 6 Feb 2018 (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.
This is a randomized, double-blind, placebo-controlled, single ascending dose study conducted at one study center in Switzerland.
Four (4) panels (A, B, C and D) of 8 male subjects (6 active and 2 placebo) each undergoing 2 investigation periods and receiving either single doses of PBTZ169 at increasing dose levels or a matching placebo.
Subjects will participate in only one panel. Blocks of 4 subjects (3 under active treatment, 1 under placebo) will be investigated in parallel. Panels A and B are interleaved.
Safety will be assessed throughout the study; serial ECGs and serial blood samples will be collected for the safety and PK assessment of PBTZ169.
Dose escalation will be allowed once the Trial Safety Board has determined that adequate safety and tolerability after panel B and panel C completion has been demonstrated to permit proceeding to the next panel.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Panel A - Active | Experimental | Drug: PBTZ169 FormulationN = 6, 10 mg then 40 mg of PBTZ169 Formulation |
| Panel A - Placebo | Placebo comparator | Drug: PlaceboN = 2, 10 mg then 40 mg of matching placebo |
| Panel B - Active | Experimental | Drug: PBTZ169 FormulationN = 6, 20 mg then 80 mg of PBTZ169 Formulation |
| Panel B - Placebo | Placebo comparator | Drug: PlaceboN = 2, 20 mg then 80 mg of matching placebo |
| Panel C - Active | Experimental | Drug: PBTZ169 Formulation, Drug: PBTZ169 NCPN = 6, First dosing of Panel C with 160 mg PBTZ169 Formulation then Second dosing of Panel C with 160 mg PBTZ169 Native Crystalline Powder (NCP) |
| Panel C - Placebo | Active comparator | Drug: PlaceboN = 2, 160 mg of matching placebo for the two interventions |
| Panel D - Active | Experimental | Drug: PBTZ169 Formulation, Drug: PBTZ169 NCPN = 6, First dosing of Panel D with 320 mg PBTZ169 Formulation then Second dosing of Panel D with 320 mg PBTZ169 Native Crystalline Powder (NCP) |
| Panel D - Placebo | Active comparator | Drug: PlaceboN = 2, 320 mg of matching placebo for the two interventions |
Who may qualify
- Ages
- 18 to 48 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Healthy male subjects aged between 18 and 48 years
- Body weight (BW) ranging between 55 and 95 kg, providing body mass index (BMI) is between 18 and 28 kg/m2
- Absence of significant findings in the medical history and physical examination as judged by the Investigator, especially for cardiovascular, pulmonary, haematological and nervous systems
- Absence of significant laboratory abnormalities as judged by the Investigator. Gilbert's syndrome (increased total and unconjugated bilirubin when fasting) will be accepted if mild
- Absence of clinically significant abnormalities on 12-lead ECG
Key exclusion criteria (22 listed)
- History of major cardiovascular, pulmonary, hepatic, immunological, renal, haematological, gastrointestinal, genitourinary, neurological, or rheumatologic disorders
- Active diseases of any type, including inflammatory disorders and infections. Mild acne is permissible providing no systemic or local treatment is provided or planned (except for cleaning lotions)
- History of significant allergy or asthma. Allergic rhinitis or conjunctivitis is acceptable if non-symptomatic when starting the study and if symptoms are not anticipated to occur during the study to a point that would require corticosteroid therapy (e.g. in case of annual use)
- History of cardiovascular dysfunction if considered as clinically relevant (conduction abnormality, arrhythmia, bradycardia, angina pectoris, cardiac hypertrophy unless elicited by training, pulmonary embolism)
- Hypertension defined as supine blood pressure >150/90 mmHg or recurrent hypotensive events considered as clinically relevant or documented orthostatic hypotension
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 |
|---|---|---|
| PBTZ169 FormulationPBTZ169 Formulation supplied as powder for oral solution | Drug | Panel A - Active, Panel B - Active, Panel C - Active, Panel D - Active |
| Placebomatching placebo supplied as powder for oral solution | Drug | Panel A - Placebo, Panel B - Placebo, Panel C - Placebo, Panel D - Placebo |
| PBTZ169 NCPPBTZ169 NCP supplied as powder for oral solution | Drug | Panel C - Active, Panel D - Active |
Primary outcome
Safety and tolerability of increasing single oral doses of PBTZ169 Formulation in healthy male adult subjects evaluated by Treatment Emergent Adverse Events (TEAEs).
Time frame: Days 0-17
Evaluation by thorough monitoring of Treatment Emergent Adverse Events (TEAEs) following doses of PBTZ169 Formulation, PBTZ169 NCP or placebo
5 secondary outcomes
Relative oral bioavailability assessment of the PBTZ169 Formulation in comparison to NCP in healthy male subjects
Time frame: Days 0-2
Pharmacokinetics (PK) of single oral doses of PBTZ169 using Cmax
Time frame: Days 0-2
Pharmacokinetics (PK) of single oral doses of PBTZ169 using Tmax
Time frame: Days 0-2
Pharmacodynamics (PD) exploration after single oral doses of PBTZ169 Formulation and NCP
Time frame: Days 0-1
Broncho-alveolar passage exploration after single oral doses of PBTZ169 Formulation and NCP (tentative)
Time frame: Days 0-1
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jul 2018.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 PBTZ169 Formulation and PBTZ169 NCP in people with Tuberculosis and Tuberculosis, Pulmonary, run by Innovative Medicines for Tuberculosis 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 9 inclusion and 22 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 13 Jul 2018. 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. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Safety and tolerability of increasing single oral doses of PBTZ169 Formulation in healthy male adult subjects evaluated by Treatment Emergent Adverse Events (TEAEs). (time frame: Days 0-17). 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 13 Jul 2018.