Healthy VolunteersPhase 1NCT04376554

Effect of Tebipenem on Normal Human Intestinal Microbiota

A Phase 1 study testing TBPM-PI-HBr and amoxicillin-clavulanate in people with Healthy Volunteers, run by Spero Therapeutics at 1 site in Sweden.

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

The overall purpose of this study is to support the development of an oral formulation of TBPM-PI-HBr by assessing the potential ecological effects of tebipenem on the normal intestinal microbiota as compared to the effects of oral amoxicillin-clavulanate. Read more about this study

Who is it for?: Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for: Healthy Volunteers
What is being tested?: TBPM-PI-HBr and amoxicillin-clavulanate
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 30 participants
Where: 1 siteSweden
Study dates: 10 Feb 2020to 6 Apr 2021
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

Healthy adult males and/or females, ≥18 years of age at the time of screening;
Medically healthy without clinically significant abnormal values for hematology, clinical chemistry, urinalysis, physical examination, vital signs, or ECG as determined by the investigator during the screening period. Discussion is encouraged between the Investigator and the Sponsor Medical Monitor regarding the clinical relevance of any abnormal laboratory value during the pre-dose period;
Willing and able to provide written informed consent;
Willing and able to comply with all study assessments and adhere to the protocol schedule, including all scheduled post-therapy visits;
Have suitable venous access for blood sampling;
Women of childbearing potential (WOCBP*) must use a highly effective form of birth control (confirmed by the Investigator). Rhythm methods will not be considered as highly effective methods of birth control. WOCBP must agree to use a highly effective method of birth control, as defined above, from signing the Informed Consent Form (ICF), throughout the study duration and until 30 days after the last dose of study drug;
Non-vasectomized male volunteers must use an adequate method of contraception (condom or condom with spermicide, depending on local regulations) from the time of signing the ICF, throughout the study duration and until 30 days after the last dose of study drug. Men with a partner who is (are) not of childbearing potential are exempt from these requirements;
Male volunteers must not donate sperm for time of signing the ICF until at least 30 days after the last dose of the study drug

Who cannot join

History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, endocrine, immunologic, dermatologic or neurological disease, including any acute illness or surgery within the past 3 months determined by the Investigator to be clinically relevant;
History or presence of known or suspected gastrointestinal disorder, including but not limited to Clostridioides difficile infection, inflammatory bowel disease, recent history of food poisoning or other stomach/intestinal disorders including gastroenteritis (within 6 months);
History of systemic antibiotic treatment during the last three months prior to randomization;
Use of any systemic prescription medication or any systemic over-the-counter medication, including herbal products and vitamins or probiotics within 7 days prior to randomization; except for hormonal contraceptives and the intermittent use of paracetamol, ibuprofen, and antihistamines;
Alanine transaminase (ALT) or aspartate transaminase (AST) >5 × upper limit of normal and CrCl of ≤50 mL/min, as estimated by the Lund-Malmö revised formula;
History of seizure disorders, except for febrile seizures in childhood;

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History of substance or alcohol abuse and positive urine drug testing at screening. History of substance or alcohol abuse and negative urine drug testing at screening can be enrolled in study based on the Investigator's discretion;
Positive for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV);
Documented or suspected hypersensitivity reaction or anaphylaxis to β-lactam antibiotics (e.g., cephalosporins, penicillins, carbapenems), product excipients (Mannitol, microcrystalline cellulose, crospovidone, magnesium stearate, colloidal silicon dioxide, and film coating systems [Opadry]) or any contraindication to the use of amoxicillin- clavulanate;
Participation in another investigational clinical study within 3 months prior to Day 1;
Current or anticipated need for systemic antibiotics, probiotics, or laxatives during the study;
Any other condition or prior therapy, which, in the opinion of the Investigator, would make the volunteer unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likely to be non-compliant with any study requirements.

Trial locations and contacts

1 site in 1 country.

Sweden1 site

Karolinska University Hospital
Huddinge, Stockholm County

Other trials in Sweden

About this study

Official title: Phase 1 Study to Evaluate the Effect of Oral Administration of Tebipenem Pivoxil Hydrobromide on Normal Human Intestinal Microbiota in Healthy Volunteers

Read the detailed description

This is a single-center, open-label, randomized, parallel-group, active-control, phase 1 study consisting of 10-day treatment period using TBPM-PI-HBr (600mg) (2× 300mg film coated tablets) or amoxicillin-clavulanate (500mg/125mg) orally every 8 hours (PO q8h [±1 hour]) in healthy volunteers. Participants will be randomized by gender to 1:1 ratio on Day 1. A maximum of 30 participants will be randomly assigned to the study treatment groups (15 in each arm) such that approximately 24 evaluable participants complete the study. Due to the multidimensional nature of data of the study, a power statement on a single endpoint is not appropriate. The main aim of the study is to estimate the effects of treatment on the intestinal microbiota, and to assess the pattern of susceptibility to specific pathogens. Based upon previous studies, a sample size of 12 participants in each group is considered sufficient to demonstrate a clinically significant impact of antibiotics on the microbiota. Total duration of study participation for each participant will be approximately 7 months.Screening visit will be performed between Day -28 to Day -1. Randomization will be performed on Day 1 and with treatment being administered from Day 1 to Day 10. Follow-up of participants will occur on Day 14, 21, 90 and 180 with appropriate visit windows. Adverse events and concomitant medications will be recorded until the end of the study (Day 180).

Conditions: Healthy Volunteers
Being tested: TBPM-PI-HBr, amoxicillin-clavulanate
Keywords: intestinal microbiota, safety, pharmacokinetics, TBPM-PI-HBr, tebipenem

What participants receive

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

TBPM-PI-HBrDrug
Also called TBPM-PI-HBr oral tablet
TBPM-PI-HBr (2 x 300mg tablets) PO q8h [±1 hour] for 10 days
amoxicillin-clavulanateDrug
Also called amoxicillin-clavulanate oral tablets
amoxicillin-clavulanate (1 × 500mg/125mg tablet) PO q8h [±1 hour] for 10 days

Study groups in NCT04376554
Study group	Role	What they receive
TBPM-PI-HBr	Experimental	Healthy subjects meeting eligibility criteria will be sequentially randomized to receive either 600mg TBPM-PI-HBr every 8 hours (PO q8h [±1 hour]) or 500/125mg amoxicillin-clavulanate PO q8h (±1 hour) for 10 days. Receives: Drug: TBPM-PI-HBr
amoxicillin-clavulanate	Active comparator	Healthy subjects meeting eligibility criteria will be sequentially randomized to receive either 500/125mg amoxicillin-clavulanate PO q8h (±1 hour) or 600mg TBPM-PI-HBr every 8 hours (PO q8h [±1 hour]) or for 10 days. Receives: Drug: amoxicillin-clavulanate

What is being measured

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

Changes in the number of microorganisms in the intestinal flora of healthy subjects during and after 10 days of oral administration of TBPM-PI-HBr or amoxicillin-clavulanate
Changes in the number of microorganisms identified in feces
Measured: Change from baseline (Day-1), at Days 2, 4, 7, 10, 14, 21, 90, and 180
Changes in the types of microorganisms in the intestinal flora of healthy subjects during and after 10 days of oral administration of TBPM-PI-HBr or amoxicillin-clavulanate
Changes in the types of microorganisms identified in feces
Measured: Change from baseline (Day-1), at Days 2, 4, 7, 10, 14, 21, 90, and 180

Secondary outcomes (7)

To explore the potential for development of resistance by measuring the number of new colonizing bacterial isolates
Emergence of resistant strains with increasing minimum inhibitory concentration values during treatment and post-treatment with tebipenem and amoxicillin-clavulanate will be determined from fecal samples.
Measured: Change from baseline (Day-1), at Days 2, 4, 7, 10, 14, 21, 90, and 180
To assess the plasma concentrations of tebipenem over 10 days of oral administration of TBPM-PI-HBr.
PK concentration of tebipenem will be measured in plasma. Concentrations of tebipenem will be plotted for each participant.
Measured: Day 1 through Day 14
To assess the fecal concentrations of tebipenem over 10 days of oral administration of TBPM-PI-HBr.
PK concentration of tebipenem will be measured in feces.Concentrations of tebipenem will be plotted for each participant.
Measured: Day 1 through Day 14
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
To assess the incidents of treatment-emergent adverse events following 10 days of oral TBPM-PI-HBr administration
Measured: Incidents of treatment-emergent adverse events from Day 1 through last follow-up visit (180 days after last dose)
Incidence of abnormal safety laboratory assessments [Safety and Tolerability]
To assess the incidents of abnormal hematology, biochemistry, coagulation and urinalysis assessments following 10 days of oral TBPM-PI-HBr administration
Measured: Incidents of abnormal safety laboratory assessments from Day 1 through last follow-up visit (180 days after last dose)
Incidence of abnormal vital sign assessments [Safety and Tolerability]
To assess the incidents of abnormal heart rate, blood pressure and body temperature assessments following 10 days of oral TBPM-PI-HBr administration
Measured: Incidents of abnormal vital sign assessments from Day 1 through last follow-up visit (180 days after last dose)
Incidence of abnormal physical exam assessments [Safety and Tolerability]
To assess the incidents of abnormal body system assessments following 10 days of oral TBPM-PI-HBr administration
Measured: Incidents of abnormal physical exam assessments from Day 1 through last follow-up visit (180 days after last dose)

Timeline

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

10 Feb 20206 Apr 2021

First posted6 May 2020
Study start10 Feb 2020
Primary completion6 Apr 2021
Study completion6 Apr 2021

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 Healthy VolunteersStudies 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: Parallel groups
Model description: Single-Center, Open-Label, Randomized, Parallel-Group, Active Control, Phase 1 Study
Masking: None (open label)
Enrolment: 30 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04376554
Sponsor's protocol ID: SPR994-103
Status last verified: May 2021
First submitted: 16 Mar 2020
Last updated: 4 May 2021
Results posted: No
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Sewunet T, Razavi M, Rosenborg S, Camporeale A, Nowak M, Melnick D, Gasink LB, Eckburg PB, Critchley IA, Nord CE, Giske CG. Effect of tebipenem pivoxil hydrobromide on the normal gut microbiota of a healthy adult population in Sweden: a randomised controlled trial. Lancet Microbe. 2024 Apr;5(4):e355-e365. doi: 10.1016/S2666-5247(23)00360-9. Epub 2024 Feb 29.
PubMed 38432233

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 4 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase 1 Study to Evaluate the Effect of Oral Administration of Tebipenem Pivoxil Hydrobromide on Normal Human Intestinal Microbiota in Healthy Volunteers
ClinicalTrials.gov ID: NCT04376554
Acronym / sponsor ID: SPR994-103
Conditions: Healthy Volunteers
Keywords: intestinal microbiota, safety, pharmacokinetics, TBPM-PI-HBr, tebipenem
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 30 participants (actual)
Lead sponsor: Spero TherapeuticsIndustry (pharma, biotech, devices)
Collaborators: IQVIA Pty Ltd
Study start: 10 Feb 2020 (actual)
Primary completion: 6 Apr 2021 (actual)
Study completion: 6 Apr 2021 (actual)
First posted: 6 May 2020 (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.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2
Model description: Single-Center, Open-Label, Randomized, Parallel-Group, Active Control, Phase 1 Study

Arm	Type	Receives
TBPM-PI-HBr	Experimental	Drug: TBPM-PI-HBrHealthy subjects meeting eligibility criteria will be sequentially randomized to receive either 600mg TBPM-PI-HBr every 8 hours (PO q8h [±1 hour]) or 500/125mg amoxicillin-clavulanate PO q8h (±1 hour) for 10 days.
amoxicillin-clavulanate	Active comparator	Drug: amoxicillin-clavulanateHealthy subjects meeting eligibility criteria will be sequentially randomized to receive either 500/125mg amoxicillin-clavulanate PO q8h (±1 hour) or 600mg TBPM-PI-HBr every 8 hours (PO q8h [±1 hour]) or for 10 days.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

Healthy adult males and/or females, ≥18 years of age at the time of screening;
Medically healthy without clinically significant abnormal values for hematology, clinical chemistry, urinalysis, physical examination, vital signs, or ECG as determined by the investigator during the screening period. Discussion is encouraged between the Investigator and the Sponsor Medical Monitor regarding the clinical relevance of any abnormal laboratory value during the pre-dose period;
Willing and able to provide written informed consent;
Willing and able to comply with all study assessments and adhere to the protocol schedule, including all scheduled post-therapy visits;
Have suitable venous access for blood sampling;

Key exclusion criteria (12 listed)

History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, endocrine, immunologic, dermatologic or neurological disease, including any acute illness or surgery within the past 3 months determined by the Investigator to be clinically relevant;
History or presence of known or suspected gastrointestinal disorder, including but not limited to Clostridioides difficile infection, inflammatory bowel disease, recent history of food poisoning or other stomach/intestinal disorders including gastroenteritis (within 6 months);
History of systemic antibiotic treatment during the last three months prior to randomization;
Use of any systemic prescription medication or any systemic over-the-counter medication, including herbal products and vitamins or probiotics within 7 days prior to randomization; except for hormonal contraceptives and the intermittent use of paracetamol, ibuprofen, and antihistamines;
Alanine transaminase (ALT) or aspartate transaminase (AST) >5 × upper limit of normal and CrCl of ≤50 mL/min, as estimated by the Lund-Malmö revised formula;

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
TBPM-PI-HBrAlso: TBPM-PI-HBr oral tabletTBPM-PI-HBr (2 x 300mg tablets) PO q8h [±1 hour] for 10 days	Drug	TBPM-PI-HBr
amoxicillin-clavulanateAlso: amoxicillin-clavulanate oral tabletsamoxicillin-clavulanate (1 × 500mg/125mg tablet) PO q8h [±1 hour] for 10 days	Drug	amoxicillin-clavulanate

Primary outcome

Changes in the number of microorganisms in the intestinal flora of healthy subjects during and after 10 days of oral administration of TBPM-PI-HBr or amoxicillin-clavulanate
Time frame: Change from baseline (Day-1), at Days 2, 4, 7, 10, 14, 21, 90, and 180
Changes in the number of microorganisms identified in feces
Changes in the types of microorganisms in the intestinal flora of healthy subjects during and after 10 days of oral administration of TBPM-PI-HBr or amoxicillin-clavulanate
Time frame: Change from baseline (Day-1), at Days 2, 4, 7, 10, 14, 21, 90, and 180
Changes in the types of microorganisms identified in feces

7 secondary outcomes

To explore the potential for development of resistance by measuring the number of new colonizing bacterial isolates
Time frame: Change from baseline (Day-1), at Days 2, 4, 7, 10, 14, 21, 90, and 180
To assess the plasma concentrations of tebipenem over 10 days of oral administration of TBPM-PI-HBr.
Time frame: Day 1 through Day 14
To assess the fecal concentrations of tebipenem over 10 days of oral administration of TBPM-PI-HBr.
Time frame: Day 1 through Day 14
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time frame: Incidents of treatment-emergent adverse events from Day 1 through last follow-up visit (180 days after last dose)
Incidence of abnormal safety laboratory assessments [Safety and Tolerability]
Time frame: Incidents of abnormal safety laboratory assessments from Day 1 through last follow-up visit (180 days after last dose)
Incidence of abnormal vital sign assessments [Safety and Tolerability]
Time frame: Incidents of abnormal vital sign assessments from Day 1 through last follow-up visit (180 days after last dose)
Incidence of abnormal physical exam assessments [Safety and Tolerability]
Time frame: Incidents of abnormal physical exam assessments from Day 1 through last follow-up visit (180 days after last dose)

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 4 May 2021.
Derived from this study: PubMed 38432233Sewunet T, Razavi M, Rosenborg S, Camporeale A, Nowak M, Melnick D, Gasink LB, Eckburg PB, Critchley IA, Nord CE, Giske CG. Effect of tebipenem pivoxil hydrobromide on the normal gut microbiota of a healthy adult population in Sweden: a randomised controlled trial. Lancet Microbe. 2024 Apr;5(4):e355-e365. doi: 10.1016/S2666-5247(23)00360-9. Epub 2024 Feb 29.
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.

Steffan Rosenborg principal investigator

Karolinska University 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 TBPM-PI-HBr and amoxicillin-clavulanate in people with Healthy Volunteers, run by Spero Therapeutics at 1 site in Sweden.

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 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 May 2021. 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 Sweden. 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?

Changes in the number of microorganisms in the intestinal flora of healthy subjects during and after 10 days of oral administration of TBPM-PI-HBr or amoxicillin-clavulanate (time frame: Change from baseline (Day-1), at Days 2, 4, 7, 10, 14, 21, 90, and 180). The study lists 2 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 NCT04376554, 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 4 May 2021.