Intra-abdominal InfectionsPhase 2NCT03354754
LYS228 PK, Clinical Response, Safety and Tolerability in Patients With Complicated Intra-abdominal Infection (cIAI)
A Phase 2 study testing LYS228 in people with Intra-abdominal Infections, run by Novartis Pharmaceuticals at 1 site in United States.
Trial summary
The purpose of the study was to evaluate whether LYS228 can be developed for the treatment of complicated intra-abdominal infections. It was planned that LYS228 exposure across patients with varying renal function would be evaluated during the study to confirm that LYS228 concentrations are predicted to be adequate to… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Intra-abdominal Infections
- What is being tested?
- LYS228
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 15 May 2018to 24 Sep 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and female patients 18 to 85 years of age with visual confirmation (presence of pus within the abdominal cavity) of an intra-abdominal infection associated with peritonitis including at least one inclusionary diagnosis during surgical intervention.
Who cannot join
- Any of the excluded diagnoses: abdominal wall abscess, small bowel obstruction, traumatic bowel perforation undergoing surgery within 12 hours, perforation of gastroduodenal ulcer with surgery within 24 hours, an intra-abdominal process that is not likely caused by infection.
- Pre-operative treatment of any duration with non-study Drug systemic antibiotic therapy for peritonitis or abscess is not allowed unless certain criteria are met.
- Concomitant bacterial infection at time of enrollment requiring non-Study Drug antibiotics and that may interfere with the evaluation of clinical response to the study antibiotic.
- Known non-abdominal source of infection, including endocarditis, osteomyelitis, abscess, meningitis, or pneumonia diagnosed within 7 days prior to enrollment.
- Patient has an Acute Physiology and Chronic Health Evaluation II (APACHE II) score > 30 or is considered, in the judgement of the investigator, unlikely to survive 4 weeks (e.g. rapidly progressive terminal illness, including septic shock).
- Patients that meet sepsis criteria as defined by the quick sequential sepsis-related organ failure assessment (qSOFA).
- Women of child-bearing potential unless they are using highly effective methods of contraception during dosing and for 7 days after stopping study treatment.
Trial locations and contacts
1 site in 1 country.
United States1 site
Novartis Investigative Site
Somers Point, New Jersey, 08230
About this study
Official title: A Randomized, Controlled, Evaluator-blinded, Multi-center Study to Evaluate LYS228 Pharmacokinetics, Clinical Response, Safety, and Tolerability in Patients With Complicated Intra-abdominal Infection
The purpose of the study was to evaluate whether LYS228 can be developed for the treatment of complicated intra-abdominal infections.
It was planned that LYS228 exposure across patients with varying renal function would be evaluated during the study to confirm that LYS228 concentrations are predicted to be adequate to treat the patient population. It was planned that the PK exposure of the initial 8 patients would be analyzed.
PK analysis was not conducted as per protocol the first analysis required 8 patients.
- Conditions
- Intra-abdominal Infections
- Being tested
- LYS228, Standard of care therapy
- Keywords
- Intra-abdominal infection, LYS228, beta-lactam antibiotics, creatinine clearance, enterobacteriaceae
- Medical subject headings
- Intraabdominal Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LYS228Drug
LYS228 IV infusion every 6 hours
Standard of care therapyDrug
IV infusion of standard of care antibiotics
| Study group | Role | What they receive |
|---|---|---|
| LYS228 | Experimental | IV infusion every 6 hours for at least 5 days Receives: Drug: LYS228 |
| Standard of care | Active comparator | IV infusion of standard of care antibiotics for at least 5 days Receives: Drug: Standard of care therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Success at Day 28
Clinical success is defined as resolution, or substantial improvement (i.e. reduction of severity of all baseline signs and symptoms and worsening of none) of all or most baseline signs and symptoms of cIAI infection without the need for additional antibiotic therapy other than any oral antibiotics given to complete treatment at home following discontinuation of Study Drug and no drainage or surgical reintervention required 96 hours after the start of Study Drug.
Measured: Day 28
Plasma Pharmacokinetics (PK) of LYS228: Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau (AUCtau)
Calculated based on LYS228 concentration in blood at different time points following drug administration on Day 5
Measured: Day 5
Plasma Pharmacokinetics (PK) of LYS228: The Observed Maximum Plasma Concentration Following Drug Administration (Cmax)
Calculated based on LYS228 concentration in blood at different time points following drug administration on Day 5
Measured: Day 5
Plasma Pharmacokinetics (PK) of LYS228: The Time to Reach the Maximum Concentration After Drug Administration (Tmax)
Calculated based on LYS228 concentration in blood at different time points following drug administration on Day 5
Measured: Day 5
Plasma Pharmacokinetics (PK) of LYS228: The Systemic (or Total Body) Clearance From Plasma Following Intravenous Administration (CL)
Calculated based on LYS228 concentration in blood at different time points following drug administration on Day 5
Measured: Day 5
Plasma Pharmacokinetics (PK) of LYS228: The Volume of Distribution at Steady State Following Intravenous Administration (Vss)
Calculated based on LYS228 concentration in blood at different time points following drug administration on Day 5
Measured: Day 5
Plasma Pharmacokinetics (PK) of LYS228: The Terminal Elimination Half-life (T1/2)
Calculated based on LYS228 concentration in blood at different time points following drug administration on Day 5
Measured: Day 5
Secondary outcomes (2)
Number of Patients With Adverse Events
Number of patients with at least one Adverse Event
Measured: Daily
Microbiological Response at Day 28
Microbiologic success at 28 days after randomization determined by microbial growth in culture from the intra-abdominal focus of infection when available or presumed eradication based on clinical success
Measured: Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Nov 2017
- Study start15 May 2018
- Primary completion24 Sep 2018
- Study completion24 Sep 2018
Why it stopped: The trial was closed as part of the out-licensure of the drug to Boston Pharmaceuticals, which will continue further clinical development of LYS228/BOS-228
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Intra-abdominal InfectionsStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe 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 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03354754
- Sponsor's protocol ID
- CLYS228X2202
- Status last verified
- Oct 2021
- First submitted
- 22 Nov 2017
- Last updated
- 11 Oct 2021
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Dean CR, Barkan DT, Bermingham A, Blais J, Casey F, Casarez A, Colvin R, Fuller J, Jones AK, Li C, Lopez S, Metzger LE 4th, Mostafavi M, Prathapam R, Rasper D, Reck F, Ruzin A, Shaul J, Shen X, Simmons RL, Skewes-Cox P, Takeoka KT, Tamrakar P, Uehara T, Wei JR. Mode of Action of the Monobactam LYS228 and Mechanisms Decreasing In Vitro Susceptibility in Escherichia coli and Klebsiella pneumoniae. Antimicrob Agents Chemother. 2018 Sep 24;62(10):e01200-18. doi: 10.1128/AAC.01200-18. Print 2018 Oct.
PubMed 30061293
Study at a glance
From the registry record, last updated by the sponsor on 11 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Controlled, Evaluator-blinded, Multi-center Study to Evaluate LYS228 Pharmacokinetics, Clinical Response, Safety, and Tolerability in Patients With Complicated Intra-abdominal Infection
- ClinicalTrials.gov ID
- NCT03354754
- Acronym / sponsor ID
- CLYS228X2202
- Conditions
- Intra-abdominal Infections
- Keywords
- Intra-abdominal infection, LYS228, beta-lactam antibiotics, creatinine clearance, enterobacteriaceae
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The trial was closed as part of the out-licensure of the drug to Boston Pharmaceuticals, which will continue further clinical development of LYS228/BOS-228
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 15 May 2018 (actual)
- Primary completion
- 24 Sep 2018 (actual)
- Study completion
- 24 Sep 2018 (actual)
- First posted
- 28 Nov 2017 (actual)
- Results
- Posted 8 Oct 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the study was to evaluate whether LYS228 can be developed for the treatment of complicated intra-abdominal infections.
It was planned that LYS228 exposure across patients with varying renal function would be evaluated during the study to confirm that LYS228 concentrations are predicted to be adequate to treat the patient population. It was planned that the PK exposure of the initial 8 patients would be analyzed.
PK analysis was not conducted as per protocol the first analysis required 8 patients.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LYS228 | Experimental | Drug: LYS228IV infusion every 6 hours for at least 5 days |
| Standard of care | Active comparator | Drug: Standard of care therapyIV infusion of standard of care antibiotics for at least 5 days |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Male and female patients 18 to 85 years of age with visual confirmation (presence of pus within the abdominal cavity) of an intra-abdominal infection associated with peritonitis including at least one inclusionary diagnosis during surgical intervention.
Key exclusion criteria (7 listed)
- Any of the excluded diagnoses: abdominal wall abscess, small bowel obstruction, traumatic bowel perforation undergoing surgery within 12 hours, perforation of gastroduodenal ulcer with surgery within 24 hours, an intra-abdominal process that is not likely caused by infection.
- Pre-operative treatment of any duration with non-study Drug systemic antibiotic therapy for peritonitis or abscess is not allowed unless certain criteria are met.
- Concomitant bacterial infection at time of enrollment requiring non-Study Drug antibiotics and that may interfere with the evaluation of clinical response to the study antibiotic.
- Known non-abdominal source of infection, including endocarditis, osteomyelitis, abscess, meningitis, or pneumonia diagnosed within 7 days prior to enrollment.
- Patient has an Acute Physiology and Chronic Health Evaluation II (APACHE II) score > 30 or is considered, in the judgement of the investigator, unlikely to survive 4 weeks (e.g. rapidly progressive terminal illness, including septic shock).
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 |
|---|---|---|
| LYS228LYS228 IV infusion every 6 hours | Drug | LYS228 |
| Standard of care therapyIV infusion of standard of care antibiotics | Drug | Standard of care |
Primary outcome
Clinical Success at Day 28
Time frame: Day 28
Clinical success is defined as resolution, or substantial improvement (i.e. reduction of severity of all baseline signs and symptoms and worsening of none) of all or most baseline signs and symptoms of cIAI infection without the need for additional antibiotic therapy other than any oral antibiotics given to complete treatment at home following discontinuation of Study Drug and no drainage or surgical reintervention required 96 hours after the start of Study Drug.
Plasma Pharmacokinetics (PK) of LYS228: Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau (AUCtau)
Time frame: Day 5
Calculated based on LYS228 concentration in blood at different time points following drug administration on Day 5
Plasma Pharmacokinetics (PK) of LYS228: The Observed Maximum Plasma Concentration Following Drug Administration (Cmax)
Time frame: Day 5
Calculated based on LYS228 concentration in blood at different time points following drug administration on Day 5
Plasma Pharmacokinetics (PK) of LYS228: The Time to Reach the Maximum Concentration After Drug Administration (Tmax)
Time frame: Day 5
Calculated based on LYS228 concentration in blood at different time points following drug administration on Day 5
Plasma Pharmacokinetics (PK) of LYS228: The Systemic (or Total Body) Clearance From Plasma Following Intravenous Administration (CL)
Time frame: Day 5
Calculated based on LYS228 concentration in blood at different time points following drug administration on Day 5
Plasma Pharmacokinetics (PK) of LYS228: The Volume of Distribution at Steady State Following Intravenous Administration (Vss)
Time frame: Day 5
Calculated based on LYS228 concentration in blood at different time points following drug administration on Day 5
Plasma Pharmacokinetics (PK) of LYS228: The Terminal Elimination Half-life (T1/2)
Time frame: Day 5
Calculated based on LYS228 concentration in blood at different time points following drug administration on Day 5
2 secondary outcomes
Number of Patients With Adverse Events
Time frame: Daily
Microbiological Response at Day 28
Time frame: Day 28
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Oct 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30061293Dean CR, Barkan DT, Bermingham A, Blais J, Casey F, Casarez A, Colvin R, Fuller J, Jones AK, Li C, Lopez S, Metzger LE 4th, Mostafavi M, Prathapam R, Rasper D, Reck F, Ruzin A, Shaul J, Shen X, Simmons RL, Skewes-Cox P, Takeoka KT, Tamrakar P, Uehara T, Wei JR. Mode of Action of the Monobactam LYS228 and Mechanisms Decreasing In Vitro Susceptibility in Escherichia coli and Klebsiella pneumoniae. Antimicrob Agents Chemother. 2018 Sep 24;62(10):e01200-18. doi: 10.1128/AAC.01200-18. Print 2018 Oct.
- A Plain Language Trial Summary is available on novartisclinicaltrials.comLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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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 2 study testing LYS228 in people with Intra-abdominal Infections, run by Novartis Pharmaceuticals at 1 site 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 1 inclusion and 7 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: stopped early, as of the sponsor's last update on 11 Oct 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 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Clinical Success at Day 28 (time frame: Day 28). 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 NCT03354754, 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 11 Oct 2021.