Study to Compare Blood Levels of Ceftriaxone Given by Suppository or Injection.

• Status: Not yet recruiting
• Trial end date: 2022-09-01
• Target enrollment: 0
• Participant gender: All

Summary

Phase 1, three-way cross-over, randomised, open label comparison of intravenous versus two rectal dosage forms of ceftriaxone in 37 healthy Thai adults.

The following regimens will be evaluated in random order in all participants:

A. Ceftriaxone (Roche ®) 500mg (slow intravenous injection) B. Ceftriaxone rectal dosage form test formulation 1 (1 x 500mg) C. Ceftriaxone rectal dosage form test formulation 2 (1 x 500mg)

Possible schedules: ABC, ACB, BAC, BCA, CAB, CBA. Each recipient will receive a single treatment dose of each of the three formulations in an order predetermined by a computer generated randomisation list. This will be a constrained randomisation which ensures approximately balanced proportions for all six schedules (either 6 or 7 patients per schedule). There will be a minimum 7 day washout period between doses. The last follow up visit is 28 (+ 2) days after final dose. Participants lost to follow-up or unevaluable for any reason before completion of pharmacokinetic sampling after the final dose will be replaced at the discretion of the investigators with another participant of the same population, if either sample size or completeness of dataset is compromised.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of Oxford
• Collaborator: Orofino Pharmaceuticals Group
• Treatments: Ceftriaxone

Criteria

Inclusion Criteria:

• Healthy male or non-pregnant female, aged 18 to 46 years (inclusive)

• Willing and able to give informed consent to participate in the trial

• Able, in the investigators opinion, and willing to comply with the study requirements and followup.

Exclusion Criteria:

• Female participant who is pregnant, lactating or planning pregnancy during the course of the study.

• Presence of any condition which in the judgment of the investigator would affect the absorption of the rectal formulation e.g. previous surgery, haemorrhoids, inflammatory bowel disease

• Irritable bowel syndrome (IBS) or diarrhoea in the 24 hours prior to study drug administration

• Presence of any condition which in the judgment of the investigator would place the participant at undue risk or interfere with the results of the study (e.g. serious underlying cardiac, renal, hepatic or neurological disease; severe malnutrition; congenital defects or febrile condition).

• Seropositive for HIV at screening

• Hepatitis B surface antigen (HBsAg) detected in serum at screening.

• Seropositive for hepatitis C virus (antibodies to HCV) at screening

• Participation in a clinical trial and/or has received a drug or a new chemical entity within 30 days or 5 half-lives, or twice the duration of the biological effect of any drug (whichever is longer) prior to the first dose of study medication and throughout the study period.

• Any medical condition that in the judgment of the investigator would make the administration of the study treatments unsafe.

• Use of medications known to have a potentially clinically significant interaction with ceftriaxone or with sodium chenodeoxycholate (Na-CDC) in the 28 days prior to the first dose and throughout the study period. This includes aluminium-containing antacids, colestipol, phenobarbital and the combined oral contraceptive pill.

• Known 27-hydroxylase deficiency (presenting as cerebrotendinous xanthomatosis)

• History of anaphylaxis and /or hypotension, laryngeal oedema, wheezing, angioedema or urticarial rash following treatment with ceftriaxone, another cephalosporin or any beta lactam (e.g. penicillin).

• History of any other clinically significant reaction to ceftriaxone, another cephalosporin or beta lactam e.g. drug induced nephritis, hepatitis, erythema multiforme that, in the opinion of the investigator, contraindicates participation in the study.

• Serious chronic illness.

• Anaemia (Hb < 10 g/dL)

• Abnormal baseline laboratory screening tests: ALT, AST, creatinine, platelet count, total WBC, out of the testing laboratory's normal range

• Hepatomegaly, right upper quadrant abdominal pain or tenderness.

• Body Mass Index> 35

• History of alcohol or substance abuse or dependence during the 6 months before study participation: History of regular alcohol consumption averaging >7 drinks/week for women or >14 drinks/week for men. One drink is equivalent to 12 g alcohol = 5 oz (150 mL) of wine or 12 oz (360 mL) of beer or 1.5 oz (45 mL) of 80 proof distilled spirits.