Bioavailability of Amoxicillin Dissolved in Human Milk

NCT01435824 | Completed Phase 2 Results

• 1 other identifier: 1000021187
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators propose to study amoxicillin absorption in a 2-stage program that will progressively produce, for the first time, information leading to pediatric pharmacology recommendations for the administration to children of amoxicillin dissolved in human milk. The investigators study will enroll adult volunteers as number of blood extractions, volume of blood required and subject availability, among other issues, generate a number of ethical and logistical constraints that make it almost impossible to carry such an intensive sampling study in infants.

Conditions

Healthy

Keywords

healthy adult volunteers; comparative bioavailability; amoxicillin; breast milk; Amoxicillin Bioavailability in breast milk

Outcome Measures

Primary Outcomes (4)

• Area Under the Curve to Time Infinity (AUC to Time Infinity)

  Amoxicillin plasma concentrations were determined by HPLC-MS/MS and AUC∞ (to time infinity) was estimated using a model-independent approach. Specifically, the log-trapezoidal method was used to calculate AUC last (AUC from time 0 to 8 h), and AUC∞ was further estimated with the elimination rate constant (Kel) of the terminal log-linear phase (β phase) of the concentration time profile extrapolating to time infinity as follows: AUC∞ = AUC last + \[C\]8h/Kel; where \[C\]8h is the plasma concentration at time 8 h postdose.

  Baseline, 0.25, 0.5, 1, 1.5, 3, 4 and 8 hours after dosing

• Area Under the Curve to 8h (AUC Last)

  Amoxicillin plasma concentrations were determined by HPLC-MS/MS and PK parameters were estimated using a model-independent approach. Specifically, the log-trapezoidal method was used to calculate AUC last (AUC from time 0 to 8 h).

  Baseline, 0.25, 0.5, 1, 1.5, 3, 4 and 8 hours after dosing

• Cmax

  A maximum plasma concentration of amoxicillin within the time frame of a dosing

  0, 0.25, 0.5, 1, 1.5, 3, 4 and 8 hours after dosing

• Tmax

  Time to reach Cmax after administration

  Data points were taken at 0, 0.25, 0.5, 1, 1.5, 3, 4 and 8 hours after dosing.

Secondary Outcomes (3)

• Elimination Half-life

  Data points were taken at 0, 0.25, 0.5, 1, 1.5, 3, 4 and 8 hours after dosing.

• Clearance/F

  Data points were taken at 0, 0.25, 0.5, 1, 1.5, 3, 4 and 8 hours after dosing.

• Volume of Distribution/F

  Data points were taken at 0, 0.25, 0.5, 1, 1.5, 3, 4 and 8 hours after dosing.

Study Arms (2)

Water as a vehicle of amoxicillin

ACTIVE COMPARATOR

Amoxicillin 500 mg was dissolved in 10 ml water and orally administered in a fasting state.

Drug: Water-dissolved amoxicillin

Human milk as a vehicle of amoxicillin

EXPERIMENTAL

Amoxicillin 500 mg was dissolved in 10 ml human milk and orally administered in a fasting state.

Drug: Human milk-dissolved amoxicillin

Interventions

Human milk-dissolved amoxicillin DRUG

An amoxicillin suspension bottle containing 5 grams of amoxicillin (powder) will be resuspended in 60 ml of breast milk to have 100mL of a 50mg/mL suspension.

Also known as: Novamoxin 250 from Novopharm, Toronto, Canada: Lot#35422063A, Frozen human milk was obtained from the Mother's Milk Bank of Ohio (USA)

Human milk as a vehicle of amoxicillin

Water-dissolved amoxicillin DRUG

An amoxicillin suspension bottle containing 5 grams of amoxicillin (powder) will be resuspended in 60 ml of water to have 100mL of a 50mg/mL suspension.

Also known as: Novamoxin 250 from Novopharm, Toronto, Canada: Lot#35422063A

Water as a vehicle of amoxicillin

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adult volunteers (\>18 and \<60 years old)
• An approximate 50% of the volunteers will be female
• Body mass index (BMI) within 18.5 to 29.9 kg/m2
• Healthy according to medical history, vital signs and a brief physical examination as determined by the principal investigator/Sub-investigators.
• Systolic blood pressure between 100-140 mmHg, inclusive and diastolic blood pressure between 60-90 mmHg, inclusive, and heart rate between 50-100 bpm, unless deemed not clinically significant by the principal investigator/Sub- investigators.
• Capable of giving written informed consent prior to receiving study medication
• Female participants will be required to fulfill at least one of the following:
• Agree to avoid pregnancy and use medically acceptable method of contraception from at least 30 days prior to the study, during the study, and until 30 days after to the study has ended (last study procedure). Medically acceptable methods of contraception include hormonal patch, implant or injection intrauterine device, or double barrier method (condom with foam or vaginal spermicidal suppository, diaphragm with spermicidal). Complete abstinence alone can be used as a method of contraception. Oral contraceptives prior to the study are acceptable as a method of contraception, but an alternative method of contraception will be required during the study and after the study has ended.
• Be surgically sterile for a minimum of 6 months
• Post menopausal for a minimum of 1 year.

You may not qualify if:

• Known history of any clinically significant hepatic (e.g. hepatic necrosis, jaundice, hepatobiliary disease), renal, gastrointestinal (e.g. peptic ulcer), cardiovascular (e.g. angina, myocardial infarction), cerebrovascular, pulmonary, endocrine (e.g. diabetes, hypophosphatemia), immunological, musculoskeletal (e.g. rhabdomyolysis, myopathy), neurological, psychiatric, dermatological, or haematological disease or condition
• History of any clinically significant illness within 30 days prior to dosing
• History of any significant physical or organ abnormality
• Known history of:
• Alcohol abuse or dependence within one year prior to drug administration
• Drug abuse or dependence
• Food allergies and/or presence of any dietary restrictions
• Severe allergic reactions (e.g. anaphylactic reactions, angioedema)
• Participation in another clinical trial or receiving an investigational drug within 30 days of the study commencement or during the study
• Use of any prescription medication within 14 days prior to drug administration (except for hormonal contraceptives)
• Use of any over the counter medications )including herbal and/or dietary supplements and/or teas) within 24 hrs prior to drug administration (except for spermicidal/barrier contraceptive products)
• Any major surgery within 6 months prior to the start of the study
• History of allergy to amoxicillin, beta-lactams or amoxicillin excipients
• History of allergy to milk, or severe lactose intolerance
• Pregnancy or lactating

Sponsors & Collaborators

• The Hospital for Sick Children: lead
• World Health Organization: collaborator

Study Sites (1)

The Hospital for Sick Children

Toronto, Ontario, M5V1X8, Canada

Location

Related Links

• Link to published study results

Limitations and Caveats

Participants ingested amoxicillin dissolved in 10 mL of milk or water. We cannot rule out that larger volumes of milk can change absorption profile of the drug. PK parameters in adults may be different from those reported in neonates and infants.

Results Point of Contact

• Title: Dr. Shinya Ito
• Organization: The Hospital for Sick Children

shinya.ito@sickkids.ca

416-813-5776

Study Officials

• Shinya Ito, MD

  The Hospital for Sick Children

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Division Head, Clinical Pharmacology and Toxicology

Model Details: Participants underwent 2 arms in a cross-over design: 1 ) amoxicillin disolved in water; and 2) amoxicillin dissolved in human milk. The order of the 2 arms were randomized.

Study Record Dates

• First Submitted: September 15, 2011
• First Posted: September 19, 2011
• Study Start: June 1, 2011
• Primary Completion: September 1, 2013
• Study Completion: October 1, 2013
• Last Updated: January 21, 2020
• Results First Posted: January 21, 2020

Record last verified: 2020-01

Locations

CA (1)