GonorrhoeaPhase 1NCT01949363
The Pharmacokinetics of Extended Duration High-dose Cefixime for the Decreased Susceptibility of Neisseria Gonorrhoeae: A Phase I Pilot Study
A Phase 1 study testing Cefixime in people with Gonorrhoea, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
This study is a Phase I, open label, non-randomized, dose-frequency escalation pharmacokinetics study among 24 healthy male and female subjects, aged 18 to 45 years to determine the pharmacokinetics and safety of high-, multi-dose cefixime for the treatment of reduced susceptibility gonorrhea. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Gonorrhoea
- What is being tested?
- Cefixime
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2013to Dec 2015
- 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 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy male or female subjects between 18 and 45 years, inclusive
- Ability to understand the consent process and procedures
- Informed consent obtained and signed
- Body mass index (BMI) < 35 kg/m^2
- Subjects agree to be available for all study visits
- Negative Breathalyzer
- Agreement by female subjects with reproductive potential to use an adequate method of contraception during the study and for 30 days after study drug administration. Female subjects must agree to the use of TWO reliable methods of contraception while receiving study drug and for 30 days after study drug administration if sexually active, which can include: condoms, spermicidal gel, diaphragm, hormonal or non-hormonal intrauterine device, surgical sterilization, oral contraceptive pill (OCP), and depot progesterone injections.
Who cannot join
- Subjects who take any prescription medication on a regular basis (except oral contraceptives, OCPs), including but not limited to, anti-psychotics, anti-depressants, anti-epileptics, cardiac medications, anti-hypertensives etc.
- Medical condition that precludes participation, including the following:
- Hypertension with confirmed systolic blood pressure >140 mmHg or confirmed diastolic blood pressure >90 mmHg, measured after 10 - 15 minutes of rest
- Morbid obesity (BMI>/=35)
- Current diagnosis of pulmonary disease
- History of or current diagnosis of diabetes
Show all 24Show fewer
- Autoimmune disorder, such as lupus, Wegener's, rheumatoid arthritis
- History of malignancy except low-grade skin cancer, (i.e., basal cell carcinoma thought to be cured)
- Known diagnosis of prolonged QT interval
- History of alcohol abuse
- History of seizure disorder
- History of renal disease
- Chronic renal, hepatic, or pulmonary disease or other condition that could interfere with the absorption of the study drug or predispose to adverse gastrointestinal events (e.g., surgical resection of significant proportions of the stomach or bowel, gastric bypass, gastric banding, irritable bowel syndrome, inflammatory bowel disease)
- Positive serology results for HIV, HBsAg, or HCV antibodies
- Subjects who have taken any prescription drugs in the previous 14 days or within 5 half-lives before dosing
- Ingestion of over the counter medications or herbal supplements within 7 days of dosing
- Positive urine toxicology for marijuana, cocaine, amphetamines, opiates, PCP, barbiturates or benzodiazepines
- History of allergic reaction or intolerance to cephalosporins
- History of allergic reaction to penicillin (all stages)
- Subjects with an allergy to macrolides may not participate in Stage 3
- Subjects with QTc >450ms (Fridericia's correction) on screening ECG may not participate in Stage 3.
- Positive pregnancy test; pregnant or nursing women
- Screening laboratory tests outside of the acceptable limits presented in Appendix C
- Any specific condition that, in the judgment of the Investigator, precludes participation because it could affect subject safety
Trial locations and contacts
1 site in 1 country.
United States1 site
Johns Hopkins Bayview Medical Center - Infectious Diseases
Baltimore, Maryland, 21224-2735
About this study
Official title: The Pharmacokinetics of Extended Duration High-Dose Cefixime for the Decreased Susceptibility of Neisseria Gonorrhoeae: A Phase I Pilot Study
This study is a Phase I, open label, non-randomized, dose-frequency escalation pharmacokinetics study among 24 healthy male and female subjects, aged 18 to 45 years to determine the pharmacokinetics and safety of high-, multi-dose cefixime for the treatment of reduced susceptibility gonorrhea. Stage 1(Cohorts A and B) will examine the pharmacokinetics of single 400mg and 800mg dose of cefixime. Stage 2(Cohorts C and D) subjects will take 800mg of cefixime every 12 hours for 2 doses. If that dosing regimen is well tolerated, the dose-frequency will escalate to 800mg every 8 hours for 3 doses, and serum levels of cefixime will be measured. Study duration is approximately 47 weeks.
Read the detailed description
This study is a Phase I, open label, non-randomized, dose-frequency escalation pharmacokinetics study among 24 healthy male and female subjects, aged 18 to 45 years to determine the pharmacokinetics and safety of high multi-dose cefixime for the treatment of reduced susceptibility gonorrhea. The study will occur in two stages as described below. Stage 1: Confirm/establish the pharmacokinetics (PK) of 400mg and 800mg doses of cefixime tablet. Stage 2: Define dosing frequency necessary to achieve total serum cefixime levels that exceed 2.0 mcg/mL for over 20 hours. Stage 1 (Cohorts A and B): Six subjects will be admitted to the Johns Hopkins Bayview Clinic Trials Unit to assess each dosing regimen, for a total of 12 subjects. At time=0, subjects will undergo baseline serum cefixime levels, followed by ingestion of cefixime. Serum collections will occur at times 0, 1, 2, 4, 8, 12, 16, 20, and 24 hours. Cohort B will have the same serum collection time points as Cohort A. Cohorts A \& B will be run nearly simultaneously as logistically feasible. Stage 2 (Cohorts C and D): After determining the PK parameters of single dose 800mg, the PK simulation model will be repeated, adjusting the model as needed based on findings from study Stage 1. Assuming there are no major discrepancies between Figure 2 (above) and the new PK simulations, the following regimens will be tested, beginning with Cohort C. Six subjects per dosing regimen, Cohorts C and D, will be admitted to the Johns Hopkins Bayview Medical Center, for a total of 12 subjects. The 800mg q12 hour x 2 regimen (Cohort C) will be tested first. For Cohort C, serum cefixime levels will be drawn at 12, 16, and 26 hours. If the q12 regimen is deemed safe and tolerable after review by the SMC, Cohort D will commence with the 800mg q8 hour x 3 regimen. Total serum cefixime levels will be drawn for Cohort D at 8, 16, 20 and 26 hours (see Section 7.2). All Stages, All Cohorts: All samples collected for PK analysis will be shipped to the University of Toledo, Dr. Jeffrey Blumer's HPLC lab for processing. Specimens will be analyzed by high performance liquid chromatography (HPLC) for total cefixime concentration levels. Targeted clinical evaluations will be used to monitor for subject reported side effects. Subjects will be asked about specific symptoms they may have experienced, including abdominal pain, nausea, vomiting, diarrhea, flatulence, headache, and rash, or any other symptoms. Additionally, subjects will be asked to maintain a Subject Diary (Appendix E) from Study Day 0 through Day 7 to record information about any symptoms experienced or medications taken. Study duration is approximately 47 weeks.
- Conditions
- Gonorrhoea
- Being tested
- Cefixime
- Keywords
- Gonococcal Infections, Cefixime, Neisseria gonorrhoeae, Azithromycin, antibiotic, cephalosporin
- Medical subject headings
- Gonorrhea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CefiximeDrug
Cefixime is an FDA approved oral semi-synthetic cephalosporin antibiotic. The standard dose (400mg), high dose (800mg and 1200mg), and multiple 800mg and 1200mg doses given over a 24-hour period using a dose-frequency escalation method. Cohort A receives 400 mg orally once, Cohort B receives 800 mg orally once; Cohort C receives 1200 mg orally once; Cohort D receives 800 mg orally 3 times (every 8 hrs)
| Study group | Role | What they receive |
|---|---|---|
| Stage 2 (Cohorts C and D) | Experimental | Cohort C will first be given 1200mg cefixime orally once; Cohort D will be given 800mg cefixime orally three times (every 8 hours); 6 subjects in each cohort Receives: Drug: Cefixime |
| Stage 1 (Cohorts A and B) | Experimental | Cohort A will be given 400mg of cefixime orally once; Cohort B will be given 800mg of cefixime given orally once; 6 subjects in each cohort Receives: Drug: Cefixime |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total serum concentrations of cefixime at multiple time points for both individuals and cohorts in total
Measured: Day 1, 2 and Day 7
Safety and tolerability assessed by laboratory monitoring, targeted clinical evaluations,: serum chemistries, liver functions tests (LFTs), hematology panel, coagulation panel, and urinalysis
Measured: Screening to Day 7
Pharmacokinetic curves of cefixime levels versus time: time to peak drug level, half-life, and elimination rate
Measured: Day 0-1, 2 and Day 7
Pharmacokinetic curves of cefixime levels versus time: total time that cefixime levels exceed 4x the MIC of 0.5 mcg/mL(serum level of 2.0 mcg/mL)
Measured: Day 0-1, 2 and Day 7
Pharmacokinetic curves of cefixime levels versus time: total area under the curve (AUC)
Measured: Day 0-1, 2 and Day 7
Pharmacokinetic curves of cefixime levels versus time: peak cefixime level.
Measured: Day 0-1, 2 and Day 7
Pharyngeal fluid concentrations of cefixime for Cohorts C - D: Cmax and ratio of fluid to serum concentration
Measured: Day 0-1
Assess subject reported adverse events, unsolicited symptoms and discomforts
Measured: Up to Day 30
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2013 (estimated)
- Study startDec 2013
- Primary completionFeb 2015
- Study completionDec 2015
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 GonorrhoeaStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01949363
- Sponsor's protocol ID
- 12-0025
- Other IDs
- HHSN272201500007I
- Status last verified
- Jun 2015
- First submitted
- 19 Sep 2013
- Last updated
- 17 Jan 2019
- Results posted
- No
Publications
Barbee LA, Nayak SU, Blumer JL, O'Riordan MA, Gray W, Zenilman JM, Golden MR, Griffiss JM. A Phase 1 Pharmacokinetic and Safety Study of Extended-Duration, High-dose Cefixime for Cephalosporin-resistant Neisseria gonorrhoeae in the Pharynx. Sex Transm Dis. 2018 Oct;45(10):677-683. doi: 10.1097/OLQ.0000000000000844.
PubMed 29624558
Study at a glance
From the registry record, last updated by the sponsor on 17 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Pharmacokinetics of Extended Duration High-Dose Cefixime for the Decreased Susceptibility of Neisseria Gonorrhoeae: A Phase I Pilot Study
- ClinicalTrials.gov ID
- NCT01949363
- Acronym / sponsor ID
- 12-0025
- Conditions
- Gonorrhoea
- Keywords
- Gonococcal Infections, Cefixime, Neisseria gonorrhoeae, Azithromycin, antibiotic, cephalosporin
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- Dec 2013
- Primary completion
- Feb 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 24 Sep 2013 (estimated)
- 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 study is a Phase I, open label, non-randomized, dose-frequency escalation pharmacokinetics study among 24 healthy male and female subjects, aged 18 to 45 years to determine the pharmacokinetics and safety of high-, multi-dose cefixime for the treatment of reduced susceptibility gonorrhea. Stage 1(Cohorts A and B) will examine the pharmacokinetics of single 400mg and 800mg dose of cefixime. Stage 2(Cohorts C and D) subjects will take 800mg of cefixime every 12 hours for 2 doses. If that dosing regimen is well tolerated, the dose-frequency will escalate to 800mg every 8 hours for 3 doses, and serum levels of cefixime will be measured. Study duration is approximately 47 weeks.
Detailed description
This study is a Phase I, open label, non-randomized, dose-frequency escalation pharmacokinetics study among 24 healthy male and female subjects, aged 18 to 45 years to determine the pharmacokinetics and safety of high multi-dose cefixime for the treatment of reduced susceptibility gonorrhea. The study will occur in two stages as described below. Stage 1: Confirm/establish the pharmacokinetics (PK) of 400mg and 800mg doses of cefixime tablet. Stage 2: Define dosing frequency necessary to achieve total serum cefixime levels that exceed 2.0 mcg/mL for over 20 hours. Stage 1 (Cohorts A and B): Six subjects will be admitted to the Johns Hopkins Bayview Clinic Trials Unit to assess each dosing regimen, for a total of 12 subjects. At time=0, subjects will undergo baseline serum cefixime levels, followed by ingestion of cefixime. Serum collections will occur at times 0, 1, 2, 4, 8, 12, 16, 20, and 24 hours. Cohort B will have the same serum collection time points as Cohort A. Cohorts A \& B will be run nearly simultaneously as logistically feasible. Stage 2 (Cohorts C and D): After determining the PK parameters of single dose 800mg, the PK simulation model will be repeated, adjusting the model as needed based on findings from study Stage 1. Assuming there are no major discrepancies between Figure 2 (above) and the new PK simulations, the following regimens will be tested, beginning with Cohort C. Six subjects per dosing regimen, Cohorts C and D, will be admitted to the Johns Hopkins Bayview Medical Center, for a total of 12 subjects. The 800mg q12 hour x 2 regimen (Cohort C) will be tested first. For Cohort C, serum cefixime levels will be drawn at 12, 16, and 26 hours. If the q12 regimen is deemed safe and tolerable after review by the SMC, Cohort D will commence with the 800mg q8 hour x 3 regimen. Total serum cefixime levels will be drawn for Cohort D at 8, 16, 20 and 26 hours (see Section 7.2). All Stages, All Cohorts: All samples collected for PK analysis will be shipped to the University of Toledo, Dr. Jeffrey Blumer's HPLC lab for processing. Specimens will be analyzed by high performance liquid chromatography (HPLC) for total cefixime concentration levels. Targeted clinical evaluations will be used to monitor for subject reported side effects. Subjects will be asked about specific symptoms they may have experienced, including abdominal pain, nausea, vomiting, diarrhea, flatulence, headache, and rash, or any other symptoms. Additionally, subjects will be asked to maintain a Subject Diary (Appendix E) from Study Day 0 through Day 7 to record information about any symptoms experienced or medications taken. Study duration is approximately 47 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Stage 2 (Cohorts C and D) | Experimental | Drug: CefiximeCohort C will first be given 1200mg cefixime orally once; Cohort D will be given 800mg cefixime orally three times (every 8 hours); 6 subjects in each cohort |
| Stage 1 (Cohorts A and B) | Experimental | Drug: CefiximeCohort A will be given 400mg of cefixime orally once; Cohort B will be given 800mg of cefixime given orally once; 6 subjects in each cohort |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Healthy male or female subjects between 18 and 45 years, inclusive
- Ability to understand the consent process and procedures
- Informed consent obtained and signed
- Body mass index (BMI) < 35 kg/m^2
- Subjects agree to be available for all study visits
Key exclusion criteria (24 listed)
- Subjects who take any prescription medication on a regular basis (except oral contraceptives, OCPs), including but not limited to, anti-psychotics, anti-depressants, anti-epileptics, cardiac medications, anti-hypertensives etc.
- Medical condition that precludes participation, including the following:
- Hypertension with confirmed systolic blood pressure >140 mmHg or confirmed diastolic blood pressure >90 mmHg, measured after 10 - 15 minutes of rest
- Morbid obesity (BMI>/=35)
- Current diagnosis of pulmonary disease
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 |
|---|---|---|
| CefiximeCefixime is an FDA approved oral semi-synthetic cephalosporin antibiotic. The standard dose (400mg), high dose (800mg and 1200mg), and multiple 800mg and 1200mg doses given over a 24-hour period using a dose-frequency escalation method. Cohort A receives 400 mg orally once, Cohort B receives 800 mg orally once; Cohort C receives 1200 mg orally once; Cohort D receives 800 mg orally 3 times (every 8 hrs) | Drug | Stage 1 (Cohorts A and B), Stage 2 (Cohorts C and D) |
Primary outcome
Total serum concentrations of cefixime at multiple time points for both individuals and cohorts in total
Time frame: Day 1, 2 and Day 7
Safety and tolerability assessed by laboratory monitoring, targeted clinical evaluations,: serum chemistries, liver functions tests (LFTs), hematology panel, coagulation panel, and urinalysis
Time frame: Screening to Day 7
Pharmacokinetic curves of cefixime levels versus time: time to peak drug level, half-life, and elimination rate
Time frame: Day 0-1, 2 and Day 7
Pharmacokinetic curves of cefixime levels versus time: total time that cefixime levels exceed 4x the MIC of 0.5 mcg/mL(serum level of 2.0 mcg/mL)
Time frame: Day 0-1, 2 and Day 7
Pharmacokinetic curves of cefixime levels versus time: total area under the curve (AUC)
Time frame: Day 0-1, 2 and Day 7
Pharmacokinetic curves of cefixime levels versus time: peak cefixime level.
Time frame: Day 0-1, 2 and Day 7
Pharyngeal fluid concentrations of cefixime for Cohorts C - D: Cmax and ratio of fluid to serum concentration
Time frame: Day 0-1
Assess subject reported adverse events, unsolicited symptoms and discomforts
Time frame: Up to Day 30
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 17 Jan 2019.
- Derived from this study: PubMed 29624558Barbee LA, Nayak SU, Blumer JL, O'Riordan MA, Gray W, Zenilman JM, Golden MR, Griffiss JM. A Phase 1 Pharmacokinetic and Safety Study of Extended-Duration, High-dose Cefixime for Cephalosporin-resistant Neisseria gonorrhoeae in the Pharynx. Sex Transm Dis. 2018 Oct;45(10):677-683. doi: 10.1097/OLQ.0000000000000844.
Related trials for Gonorrhoea
Active, not recruitingPhase 4
Periodic Presumptive Treatment vs. doxyPEP for STI Control in Kenyan MSM
Gonorrhea Male, Chlamydia (Male)
Not yet recruiting
Pilot HIV Self-Testing And Self-collected STI Testing Strategy for Sex Worker Empowerment Study
HIV, Syphilis
Not yet recruitingPhase 3
A Clinical Study to Assess the Efficacy of Weekly Doxycycline Prophylaxis to Reduce Bacterial Sexually Transmitted Infections (STI) in Young African Women
Sexually Transmitted Infection (STI), Gonorrhea
Not yet recruiting
Optimizing Antibiotic Prescription in STI Clinics Using Rapid POCT
Chlamydia Trachomatis Infection, Neisseria Gonorrhoeae Infection
RecruitingPhase 4
Doxycycline Prophylaxis for Prevention of Sexually Transmitted Infections
Gonorrhea, Chlamydia
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 Cefixime in people with Gonorrhoea, run by National Institute of Allergy and Infectious Diseases (NIAID) 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 7 inclusion and 24 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 17 Jan 2019. 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 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?
Total serum concentrations of cefixime at multiple time points for both individuals and cohorts in total (time frame: Day 1, 2 and Day 7). The study lists 8 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 NCT01949363, 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 17 Jan 2019.