Antibiotic ToxicityPhase 1NCT05359627
A Pharmacokinetic Study of Polymyxin B in Healthy Subjects and Subjects With Renal Insufficiency
A Phase 1 study testing Polymyxin B in people with Antibiotic Toxicity, run by TTY Biopharm at 1 site in Taiwan.
Trial summary
This is an open-label, single-center, single-dose, parallel-group study to evaluate the PK and safety profiles of polymyxin B administered by IV infusion in healthy subjects and subjects with renal insufficiency. Read more about this study
- Who is it for?
- Ages 20 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Antibiotic Toxicity
- What is being tested?
- Polymyxin B
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteTaiwan
- Study dates
- 26 Jul 2022to 3 Mar 2023
- 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 20 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male and female subjects between 20 and 70 years of age (inclusive) at screening.
- Subjects with Body Mass Index (BMI) between 18.5 and 35 kg/m² (inclusive) at screening.
- Subjects with sitting heart rate between 60 and 100 beats/min at screening.
- Subjects with serum albumin between 3.5 and 5.7 g/dL (inclusive).
- Subjects (normal renal function group) with creatinine clearance (CLcr) ≥ 90 mL/min at screening; Subjects (mild renal insufficiency group) with CLcr between 60 and 89 mL/min (inclusive) within 3 months prior to screening and at screening; Subjects (long-term IHD group) with ESRD receiving IHD therapy 3 times a week for at least 3 months prior to dosing of study drug.
- Female subjects with childbearing potential must have a negative serum pregnancy test at screening and pregnancy test on Day -1.
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- Subjects with sufficient peripheral vascular access for blood collection.
- Subject is willing and able to comply with all study procedures and restrictions.
- Subject understands the study procedures and is willing and able to provide written informed consent.
Who cannot join
- Arm 1 (normal renal function group): Subject with history or presence of any clinically significant cardiovascular, respiratory, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, psychiatric disease or disorder, with active bleeding or with head injury or meningitis 3 months prior to dosing, in the opinion of the investigator or any uncontrolled medical illness which in the opinion of the investigator would jeopardize the safety of the subject, interfere with study assessments, or impact the validity of the study results; Arm 2 (mild renal insufficiency group): Subject with history or presence of any clinically significant cardiovascular, respiratory, hepatic, hematological, immunologic, neurological, psychiatric disease, active bleeding within 3 months, congenital renal disease (e.g., polycystic kidney disease) or disorder, with head injury or meningitis 3 months prior to dosing, in the opinion of the investigator or any uncontrolled medical illness which in the opinion of the investigator would jeopardize the safety of the subject, interfere with study assessments, or impact the validity of the study results; Arm 3 (long-term IHD group): Subject with history or presence of any clinically significant respiratory, hepatic, hematological, immunologic, neurological, psychiatric disease, active bleeding within 3 months, congenital renal disease (e.g., polycystic kidney disease) or disorder, with head injury or meningitis 3 months prior to dosing, in the opinion of the investigator or any uncontrolled medical illness which in the opinion of the investigator would jeopardize the safety of the subject, interfere with study assessments, or impact the validity of the study results.
- Known history of or positive screening result for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen (HBsAg), or hepatitis C virus antibody (HCVAb).
- Subject has a positive test result for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) viral RNA test on Day -1.
- Subject who has a known, or suspected allergy, or sensitivity to polymyxins (colistin, polymyxin B) antibiotics in the opinion of the investigator.
- Subject with current evidence or history of malignancy in the 1 year prior to Day -1.
- Subject who has received polymyxins (colistin, polymyxin B) treatment within 28 days prior to Day -1.
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- Use of prohibited medications of this study within 28 days (or 5 half-lives, if longer) prior to Day -1.
- Subjects with a QT interval corrected using Fridericia's formula (QTcF) prolongation over 500 milliseconds or history of prolonged QT syndrome at screening.
- Subject who used other investigational medicine within 28 days prior to the screening visit or plan to use other investigational medicine during the study period.
- Donation of blood within 56 days or plasma within 14 days prior to the screening visit or plan to donate during the entire study period.
- Blood transfusion within 14 days prior to the screening visit or necessary for regular blood transfusion within 3 months prior to the screening visit.
- Reports of a history of substance or alcohol abuse within 1 year prior to the screening visit.
- Female subject who is currently pregnant or breastfeeding or plans to be pregnant during the study period.
- Unstable or new medical conditions in the 3 months prior to screening.
- Any condition determined by the investigator to be unsuitable for subject enrollment.
Trial locations and contacts
1 site in 1 country.
About this study
This is an open-label, single-center, single-dose, parallel-group study to evaluate the PK and safety profiles of polymyxin B administered by IV infusion in healthy subjects and subjects with renal insufficiency.
Read the detailed description
The study will enroll approximately 24 adult subjects in the following three Arms based on renal function. Approximately 8 subjects for each Arm are planned to be enrolled to fulfill the analysis of at least 6 evaluable subjects in each Arm. The subject who drops out of the study may be replaced at the discretion of the Sponsor.
- Arm 1 (normal renal function group): Subjects with CLcr ≥ 90 mL/min
- Arm 2 (mild renal insufficiency group): Subjects with CLcr between 60 and 89 mL/min (inclusive)
- Arm 3 (long-term IHD group): Subjects with ESRD receiving IHD therapy 3 times a week for at least 3 months prior to dosing of study drug; Subjects will receive a single dose of polymyxin B one day after his/her 3rd dialysis of the week.
- Conditions
- Antibiotic Toxicity
- Being tested
- Polymyxin B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Polymyxin BDrug
Polymyxin B acts against gram-negative bacteria (GNB) only, via three known mechanisms of action: First, polymyxin B can electrostatically interact with the outer membranes of GNB to compete against and displace calcium and magnesium divalent cations from membrane lipids, thereby disrupting lipopolysaccharide (LPS) molecules on the outer membrane and triggering their release. This leads to changes in the permeability of the bacterial membrane and subsequently causes cell content leakage, cell lysis, and death. Second, polymyxin B can act as a surfactant, as it is amphipathic and contains both lipophilic and lipophobic groups; this allows it to penetrate cell membranes, interact with the phospholipids within, and rapidly disrupt membranes to kill bacteria. Third, polymyxin B can bind to the lipid A portion of bacterial endotoxin or LPS molecules, thus neutralizing their toxicity.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | normal renal function group Receives: Drug: Polymyxin B |
| Arm 2 | Experimental | mild renal insufficiency group Receives: Drug: Polymyxin B |
| Arm 3 | Experimental | long-term IHD group Receives: Drug: Polymyxin B |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cmax
Cmax: Maximum observed plasma concentration
Measured: Baseline,48hours
AUC0-last
AUC0-last: Area under the plasma concentration vs time curve from time 0 to the last measurable concentration
Measured: Baseline,48hours
AUC0-inf
AUC0-inf: Area under the plasma concentration vs time curve from time 0 extrapolated to infinity
Measured: Baseline,48hours
CL
CL: Clearance, calculated as Dose/AUC0-inf
Measured: Baseline,48hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2022
- Study start26 Jul 2022
- Primary completion3 Mar 2023
- Study completion3 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Antibiotic ToxicityStudies 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
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- TTY Biopharm
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Fang, Principal investigator, Shin Kong Memorial Wu Ho-Su Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05359627
- Sponsor's protocol ID
- TTYPX2201
- Status last verified
- Apr 2023
- First submitted
- 29 Mar 2022
- Last updated
- 27 Apr 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: No individual participant data(IPD) sharing plan
Publications
Fang YW, Huang CH, Jang TN, Lin SS, Wang JT, Huang YT, Tsai MH. Pharmacokinetic study of polymyxin B in healthy subjects and subjects with renal insufficiency. Clin Transl Sci. 2024 Dec;17(12):e70110. doi: 10.1111/cts.70110.
PubMed 39673151
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pharmacokinetic Study of Polymyxin B in Healthy Subjects and Subjects With Renal Insufficiency
- ClinicalTrials.gov ID
- NCT05359627
- Acronym / sponsor ID
- TTYPX2201
- Conditions
- Antibiotic Toxicity
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- TTY BiopharmIndustry (pharma, biotech, devices)
- Study start
- 26 Jul 2022 (actual)
- Primary completion
- 3 Mar 2023 (actual)
- Study completion
- 3 Mar 2023 (actual)
- First posted
- 4 May 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.
This is an open-label, single-center, single-dose, parallel-group study to evaluate the PK and safety profiles of polymyxin B administered by IV infusion in healthy subjects and subjects with renal insufficiency.
Detailed description
The study will enroll approximately 24 adult subjects in the following three Arms based on renal function. Approximately 8 subjects for each Arm are planned to be enrolled to fulfill the analysis of at least 6 evaluable subjects in each Arm. The subject who drops out of the study may be replaced at the discretion of the Sponsor.
- Arm 1 (normal renal function group): Subjects with CLcr ≥ 90 mL/min
- Arm 2 (mild renal insufficiency group): Subjects with CLcr between 60 and 89 mL/min (inclusive)
- Arm 3 (long-term IHD group): Subjects with ESRD receiving IHD therapy 3 times a week for at least 3 months prior to dosing of study drug; Subjects will receive a single dose of polymyxin B one day after his/her 3rd dialysis of the week.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: Polymyxin Bnormal renal function group |
| Arm 2 | Experimental | Drug: Polymyxin Bmild renal insufficiency group |
| Arm 3 | Experimental | Drug: Polymyxin Blong-term IHD group |
Who may qualify
- Ages
- 20 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Male and female subjects between 20 and 70 years of age (inclusive) at screening.
- Subjects with Body Mass Index (BMI) between 18.5 and 35 kg/m² (inclusive) at screening.
- Subjects with sitting heart rate between 60 and 100 beats/min at screening.
- Subjects with serum albumin between 3.5 and 5.7 g/dL (inclusive).
- Subjects (normal renal function group) with creatinine clearance (CLcr) ≥ 90 mL/min at screening; Subjects (mild renal insufficiency group) with CLcr between 60 and 89 mL/min (inclusive) within 3 months prior to screening and at screening; Subjects (long-term IHD group) with ESRD receiving IHD therapy 3 times a week for at least 3 months prior to dosing of study drug.
Key exclusion criteria (15 listed)
- Arm 1 (normal renal function group): Subject with history or presence of any clinically significant cardiovascular, respiratory, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, psychiatric disease or disorder, with active bleeding or with head injury or meningitis 3 months prior to dosing, in the opinion of the investigator or any uncontrolled medical illness which in the opinion of the investigator would jeopardize the safety of the subject, interfere with study assessments, or impact the validity of the study results; Arm 2 (mild renal insufficiency group): Subject with history or presence of any clinically significant cardiovascular, respiratory, hepatic, hematological, immunologic, neurological, psychiatric disease, active bleeding within 3 months, congenital renal disease (e.g., polycystic kidney disease) or disorder, with head injury or meningitis 3 months prior to dosing, in the opinion of the investigator or any uncontrolled medical illness which in the opinion of the investigator would jeopardize the safety of the subject, interfere with study assessments, or impact the validity of the study results; Arm 3 (long-term IHD group): Subject with history or presence of any clinically significant respiratory, hepatic, hematological, immunologic, neurological, psychiatric disease, active bleeding within 3 months, congenital renal disease (e.g., polycystic kidney disease) or disorder, with head injury or meningitis 3 months prior to dosing, in the opinion of the investigator or any uncontrolled medical illness which in the opinion of the investigator would jeopardize the safety of the subject, interfere with study assessments, or impact the validity of the study results.
- Known history of or positive screening result for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen (HBsAg), or hepatitis C virus antibody (HCVAb).
- Subject has a positive test result for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) viral RNA test on Day -1.
- Subject who has a known, or suspected allergy, or sensitivity to polymyxins (colistin, polymyxin B) antibiotics in the opinion of the investigator.
- Subject with current evidence or history of malignancy in the 1 year prior to Day -1.
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 |
|---|---|---|
| Polymyxin BPolymyxin B acts against gram-negative bacteria (GNB) only, via three known mechanisms of action: First, polymyxin B can electrostatically interact with the outer membranes of GNB to compete against and displace calcium and magnesium divalent cations from membrane lipids, thereby disrupting lipopolysaccharide (LPS) molecules on the outer membrane and triggering their release. This leads to changes in the permeability of the bacterial membrane and subsequently causes cell content leakage, cell lysis, and death. Second, polymyxin B can act as a surfactant, as it is amphipathic and contains both lipophilic and lipophobic groups; this allows it to penetrate cell membranes, interact with the phospholipids within, and rapidly disrupt membranes to kill bacteria. Third, polymyxin B can bind to the lipid A portion of bacterial endotoxin or LPS molecules, thus neutralizing their toxicity. | Drug | Arm 1, Arm 2, Arm 3 |
Primary outcome
Cmax
Time frame: Baseline,48hours
Cmax: Maximum observed plasma concentration
AUC0-last
Time frame: Baseline,48hours
AUC0-last: Area under the plasma concentration vs time curve from time 0 to the last measurable concentration
AUC0-inf
Time frame: Baseline,48hours
AUC0-inf: Area under the plasma concentration vs time curve from time 0 extrapolated to infinity
CL
Time frame: Baseline,48hours
CL: Clearance, calculated as Dose/AUC0-inf
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 27 Apr 2023.
- Derived from this study: PubMed 39673151Fang YW, Huang CH, Jang TN, Lin SS, Wang JT, Huang YT, Tsai MH. Pharmacokinetic study of polymyxin B in healthy subjects and subjects with renal insufficiency. Clin Transl Sci. 2024 Dec;17(12):e70110. doi: 10.1111/cts.70110.
- Individual participant dataSharing planned: No. No individual participant data(IPD) sharing plan
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.
Fang principal investigator
Shin Kong Memorial Wu Ho-Su Hospital
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 Polymyxin B in people with Antibiotic Toxicity, run by TTY Biopharm at 1 site in Taiwan.
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 15 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 27 Apr 2023. 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 Taiwan. 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?
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?
Cmax (time frame: Baseline,48hours). The study lists 4 primary outcomes in all. 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 NCT05359627, 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 27 Apr 2023.