Evaluating cefixime for the prevention of congenital syphilis: a single-dose pharmacokinetic study (Study 1 of 3)
Evaluating cefixime for the prevention of congenital syphilis: a single-dose pharmacokinetic study in pregnant Papua New Guinean women (Study 1 of 3)
World Health Organization
64 participants
Nov 10, 2025
Interventional
Conditions
Summary
There is an urgent need for new treatments for syphilis in pregnancy to prevent congenital syphilis. Benzathine penicillin G (BPG; 2.4 MU) is currently the only recommended treatment for pregnant patients to treat maternal syphilis and prevent congenital syphilis, however global challenges with BPG supply and distribution have led to recurrent global shortages which have compounded the local challenges of poor adherence and low acceptability of intramuscular (IM) BPG. Cefixime, an oral broad-spectrum cephalosporin, may be an effective alternative to IM BPG for treatment of syphilis and prevention of congenital syphilis. There is little data on the pharmacology of cefixime in pregnancy, and no comprehensive pharmacokinetic studies have been performed in pregnant women, justifying detailed pharmacokinetic safety and dose finding studies prior to further deployment of this alternative treatment strategy. The overall aim of this research is to inform the suitability and optimal dosing strategy for cefixime as an alternative treatment to BPG for antenatal syphilis, which will be determined through the undertaking of a series of pharmacokinetic studies (Study 1-3). Study 1, a pharmacokinetic study of single dose cefixime in pregnant and nonpregnant Papua New Guinean women, aims to define the pharmacokinetic disposition of cefixime in pregnancy, and the role of fat in bioavailability and drug clearance. Data generated within this study will inform population pharmacokinetic model development, informing multiple dose strategies (Study 2) and simulations of expected maternal/foetal transfer (to be confirmed in Study 3). The effect of food on cefixime pharmacokinetics will also be evaluated in healthy non-pregnant women), to inform if future dosing strategies should co-administer drug with fat (e.g. full-cream milk) to improve drug absorption and bioavailability.
Eligibility
Inclusion Criteria20
- Pregnant participants
- a) In the second or third trimester of pregnancy (14-38 weeks gestation).
- b) >/=18 years of age at time of enrolment
- c) Provides informed consent (including verbal consent from husband/father, as culturally appropriate, should the woman feel appropriate)
- d) Tested negative for syphilis and HIV
- e) No signs of malaria or other significant concomitant disease
- f) Haemoglobin concentration >10 g/dL
- g) No known allergies to penicillin or cephalosporins – confirmed through verbal reporting and review of woman’s health book for evidence of medical documentation.
- h) No history of complicated pregnancies
- i) Agreement to attend all study visits.
- Nonpregnant participants
- Volunteer nonpregnant women will be sought from the community. 'Best matches' will be selected based on age (1:1 comparison with the age of each pregnant participant). Nonpregnant volunteers will be able to participate if they meet the following criteria.
- a) >/= 18 years of age at time of enrolment
- b) Provides informed consent
- c) Tested negative for pregnancy
- d) Tested negative for syphilis and HIV (as documented in participant health book; testing conducted as part of sexual health clinic procedures)
- e) No signs of malaria or other significant concomitant disease
- f) Haemoglobin concentration >10 g/dL
- g) No known allergies to penicillin or cephalosporins – confirmed through verbal reporting and review of woman’s health book for evidence of medical documentation.
- h) Agreement to attend all study visits.
Exclusion Criteria19
- Pregnant participants
- a) Are not in the second or third trimester of pregnancy (14-38 weeks gestation).
- b) < 18 years of age at time of enrolment
- c) Does not provide informed consent (including verbal consent from husband/father, as culturally appropriate, should the woman feel appropriate)
- d) Tested positive for syphilis and HIV (as documented in participant health book; testing conducted as part of routine antenatal care prior to study screening procedures)
- e) Has signs of malaria or other significant concomitant disease
- f) Haemoglobin concentration <10 g/dL
- g) Is allergic to penicillin or cephalosporins – confirmed through verbal reporting and review of woman’s health book for evidence of medical documentation.
- h) History of complicated pregnancies
- i) Does not agree to attend all study visits.
- Nonpregnant women
- a) <18 years of age at time of enrolment
- b) Does not provide informed consent
- c) Tested positive for pregnancy
- d) Tested positive for syphilis and HIV
- e) Has signs of malaria or other significant concomitant disease
- f ) Haemoglobin concentration <10 g/dL
- g) Has allergies to penicillin or cephalosporins – confirmed through verbal reporting and review of woman’s health book for evidence of medical documentation.
- h) Does not agree to attend all study visits.
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Interventions
Arm 1: Healthy pregnant women (14-38 weeks gestation): Single dose 400mg oral Cefixime Arm 2: Healthy non-pregnant women: Single dose 400mg oral Cefixime with fat (9% fat; cross-over study). For each dose, participants will receive a single 400 mg oral capsule of cefixime with water, with the exact time of dosing noted in the participant's case report form. All single-dose treatments will be administered as directly observed treatment, and confirmed through pharmacokinetic evaluation (drug concentrations). For participants in Arm B, each participant will be randomised to one of two treatment sequences (A or B), where they will receive a single dose of 400 mg cefixime on two occasions, one in the fasting state (control group) and the other in the fed state (exposure group) with a wash-out period of a minimum of 72 hours between doses. For those who are administered cefixime in a fed state (exposure group), they will be administered their dose of cefixime within 15-minutes of eating a Papua New Guinean breakfast; including sweet potato (or similar starch), sago cooked in coconut milk, flavoured cracker biscuits and/or tinned meat (volume and type of food consumed based on participant preference; but documented in case report form). A full tetra-pack of chocolate flavoured milk (250mL) will be drunk alongside the meal to ensure adequate exposure to fat.
Locations(1)
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ACTRN12625001180404