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Renal ImpairmentPhase 1NCT04178577

Phase 1 Study of PK and Safety of Tebipenem Pivoxil Hydrobromide (TBPM-PI-HBr) in Subjects With Various Degrees Of Renal Function

A Phase 1 study testing Tebipenem pivoxil hydrobromide (TBPM-PI-HBr) in people with Renal Impairment, run by Spero Therapeutics at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Evaluation of the pharmacokinetics (PK) of TBPM-PI-HBr in subjects with normal renal function, subjects with various degrees of renal insufficiency, and subjects with end-stage renal disease (ESRD) receiving hemodialysis (HD) therapy. Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for
Renal Impairment
What is being tested?
Tebipenem pivoxil hydrobromide (TBPM-PI-HBr)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
39 participants
Where
2 sitesUnited States
Study dates
6 Dec 2019to 11 Sep 2020
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 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Adult males or females, 18 years of age or older.
  • BMI ≥ 18.5 and ≤ 39.9 (kg/m2) and weight between 50.0 and 130.0 kg
  • Medically healthy without clinically significant abnormalities (Healthy Volunteers) or medically stable without clinically significant acute or chronic illness (Subjects with Renal Disease).
  • Non-smoker for at least 1 month prior to screening for the study.
  • Ability and willingness to abstain from alcohol, caffeine, xanthinecontaining beverages or food.

Who cannot join

  • Any clinically significant medical history or abnormal findings upon physical examination, or clinical laboratory tests, not specifically excluded in other criteria below that, in the opinion of the Investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject.
  • Electrocardiogram (ECG) with QTcF interval duration equal or greater than 500 msec
  • Hemoglobin (HB), hematocrit (HCT), white blood cell count (WBC), or platelet count less than the lower limit of normal range of the reference laboratory (Cohort 1). HB < 8.5 gm/dL, WBC ≤ 3,000 cells/μL or platelet count ≤ 100,000 cells/μL (Cohorts 2-5).
  • Results of biochemistry tests for alanine aminotransferase (ALT), aspartate aminotransferase (AST) and bilirubin greater than 1.5 X the upper limit of normal (ULN) for the reference laboratory.
  • Recent history of known or suspected Clostridium difficile infection.
  • History of known genetic metabolism anomaly associated with carnitine deficiency (e.g., carnitine transporter defect, methylmalonic aciduria, propionic academia).
Show all 13Show fewer
  • History of chronic liver disease, cirrhosis, or biliary disease.
  • History of seizure disorder except childhood history of febrile seizures.
  • Positive urine drug/alcohol testing.
  • Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C (HCV) antibodies.
  • History of substance abuse or alcohol abuse.
  • Use of antacids within 24 hours prior to study drug administration.
  • Known history of clinically significant hypersensitivity reaction or anaphylaxis to any medication.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Medical Facility

    Miami, Florida, 33136

  • Medical Facility

    Orlando, Florida, 32809

Other trials in United States

About this study

Official title: A Phase 1, Open-Label Study to Assess the Pharmacokinetics and Safety of Orally Administered Tebipenem Pivoxil Hydrobromide (TBPM-PI-HBr) in Subjects With Various Degrees of Renal Function

Evaluation of the pharmacokinetics (PK) of TBPM-PI-HBr in subjects with normal renal function, subjects with various degrees of renal insufficiency, and subjects with end-stage renal disease (ESRD) receiving hemodialysis (HD) therapy.

Being tested
Tebipenem pivoxil hydrobromide (TBPM-PI-HBr)
Keywords
End State Renal Disease (ESRD), Renal Insufficiency, Renal Impairment, Renal Disease, Hemodialysis
Medical subject headings
Renal Insufficiency, Kidney Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Tebipenem pivoxil hydrobromide (TBPM-PI-HBr)Drug

    Also called TBPM-PI-HBr, SPR994

    Tebipenem pivoxil hydrobromide (TBPM-PI-HBr) 600 mg single-dose given orally.

Study groups in NCT04178577
Study groupRoleWhat they receive
Tebipenem pivoxil hydrobromide (TBPM-PI-HBr)ExperimentalTebipenem pivoxil hydrobromide (TBPM-PI-HBr) 600 mg single-dose given orally.
Receives: Drug: Tebipenem pivoxil hydrobromide (TBPM-PI-HBr)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Apparent total body clearance (CL/F).

    Measured: 72 hours post dose

  2. Area under the curve from time zero to the last quantifiable sample (AUC0-last).

    Measured: 72 hours post dose

  3. Area under the curve extrapolated to infinity (AUC0-∞).

    Measured: 72 hours post dose

  4. Apparent steadystate volume of distribution (Vss/F).

    Measured: 72 hours post dose

  5. Maximum plasma concentration (Cmax).

    Measured: 72 hours post dose

  6. Time to the maximum plasma concentration (Tmax).

    Measured: 72 hours post dose

  7. Terminal elimination half-life (t1/2).

    Measured: 72 hours post dose

Secondary outcomes (11)

  1. Incidence of treatment-emergent AEs (including SAEs) categorized by severity and relationship to study drug.

    AEs will be categorized by system organ class (SOC) and AE preferred term (PT).

    Measured: 14 days post last dose

  2. Significant changes from baseline in clinical laboratory values.

    All laboratory data will be summarized by cohort, and at each scheduled time-point using descriptive statistics (n, mean, SD, median, minimum, and maximum).

    E.g. of laboratory values: hematology, biochemistry, coagulation and urinalysis

    Measured: 14 days post last dose

  3. Significant changes from baseline in physical examination.

    Changes in baseline in physical examination findings (Normal, Abnormal NCS, Abnormal CS) will be summarized using counts and percentages by cohort, and will also be listed individually for each scheduled time-point.

    Physical examination will include: HEENT; cardiovascular, respiratory, gastrointestinal, dermatological, musculoskeletal, nervous systems, lymph nodes and general appearance. Additional body systems may be evaluated at the Investigator's discretion.

    Measured: 14 days post last dose

  4. Significant changes from baseline in vitals signs.

    Vital sign values and changes from baseline at each scheduled time-point will be summarized by cohort for the Safety Analysis Population using descriptive statistics (n, mean, SD, median, minimum, and maximum).

    Vitals signs will include: systolic and diastolic blood pressure, heart rate, respiratory rate, and temperature.

    Measured: 14 days post last dose

  5. Significant changes from baseline in ECG

    Overall evaluation of safety ECGs will be summarized by cohort, using frequency counts and percentage of subjects as normal or abnormal, and the relevance of the abnormality will be summarized by CS or NCS.

    ECG parameters will include: heart rate, RR interval, PR interval, QRS, QT and QTcF

    Measured: 14 days post last dose

  6. Renal clearance (CLR)

    Measured: 72 hours post dose

  7. Fraction of drug excreted in the urine expressed as a percentage of the TBPM-PI-HBr dose administered (Ae%).

    Measured: 72 hours post dose

  8. Amount of drug excreted in the urine through 24 hours (Ae0-24), through 48 hours (Ae0-48) and through 72 hours (Ae0-72) for Cohorts 1-4.

    Measured: 72 hours post dose

  9. For subjects on dialysis, estimated hemodialysis clearance (CLHD) will be assessed.

    Measured: Up to 1 day post dose - between start and end of hemodialysis.

  10. For subjects on dialysis, the extraction ratio (ER) will be assessed.

    Measured: Up to 1 day post dose - between start and end of hemodialysis.

  11. For subjects on dialysis, the amount of the dose removed by hemodialysis (XHD) will be assessed.

    Measured: Up to 1 day post dose - between start and end of hemodialysis.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Nov 2019
  2. Study start6 Dec 2019
  3. Primary completion6 Sep 2020
  4. Study completion11 Sep 2020

Resources

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
39 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04178577
Sponsor's protocol ID
SPR994-102
Status last verified
Dec 2019
First submitted
14 Nov 2019
Last updated
27 Nov 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Patel G, Rodvold KA, Gupta VK, Bruss J, Gasink L, Bajraktari F, Lei Y, Jain A, Srivastava P, Talley AK. Pharmacokinetics of Oral Tebipenem Pivoxil Hydrobromide in Subjects with Various Degrees of Renal Impairment. Antimicrob Agents Chemother. 2022 May 17;66(5):e0240721. doi: 10.1128/aac.02407-21. Epub 2022 Apr 14.

    PubMed 35420493

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Tebipenem pivoxil hydrobromide (TBPM-PI-HBr) in people with Renal Impairment, run by Spero Therapeutics at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 13 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 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. 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?

Apparent total body clearance (CL/F). (time frame: 72 hours post dose). The study lists 7 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 NCT04178577, 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 Nov 2020.

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