HealthyPhase 2NCT01435824
Bioavailability of Amoxicillin Dissolved in Human Milk
A Phase 2 study testing Human milk-dissolved amoxicillin and Water-dissolved amoxicillin in people with Healthy, run by The Hospital for Sick Children at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Human milk-dissolved amoxicillin and Water-dissolved amoxicillin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteCanada
- Study dates
- Jun 2011to Oct 2013
- 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 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
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- Smoking is not an exclusion criterion but we will identify smokers.
- 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.
Who cannot join
- 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
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- 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
- Conditions associated with malabsorption
- Taking any form of antacids as they may increase the risk of orally transmitted viruses from human milk.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Bioavailability of Amoxicillin Dissolved in Human Milk: An Adult Volunteer Study as a First Step Towards Defining Drug Doses for Infants
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.
Read the detailed description
As recommended by the Expert Committee on Selection and Use of Essential Medicines, WHO (http://www.who.int/selection_medicines/committees/en/index.html), oral solid formulations are the preferred forms of medicines for children, especially in developing countries, because of relatively inexpensive and less complicated manufacturing, transporting and storage processes. Whereas solid dosage forms are advantageous in these pharmaceutical logistics, administering solid formulations to infants and children is a challenging issue. Dissolving medicines in water may be acceptable, but safety of drinking water for infants in developing countries and water solubility of the drug itself are major concerns. These challenges are exemplified in the treatment of infectious diseases and diarrhea in infants. Commonly used drugs for infants in low income settings include antibiotics such as amoxicillin. Expert sources have suggested that drug administration in breast milk may be effective. However, little data is currently available to support the recommendation to administer medications dissolved in breast milk to infants.
The second stage of the project will use the information obtained from the first stage, combined with pre-existing data, to define a rational dosing schedule of the target drug dissolved in human milk for young children, using population PK modeling and simulation. This is a study in silico.
- Conditions
- Healthy
- Being tested
- Human milk-dissolved amoxicillin, Water-dissolved amoxicillin
- Keywords
- healthy adult volunteers, comparative bioavailability, amoxicillin, breast milk, Amoxicillin Bioavailability in breast milk
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Human milk-dissolved amoxicillinDrug
Also called Novamoxin 250 from Novopharm, Toronto, Canada: Lot#35422063A, Frozen human milk was obtained from the Mother's Milk Bank of Ohio (USA)
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.
Water-dissolved amoxicillinDrug
Also called Novamoxin 250 from Novopharm, Toronto, Canada: Lot#35422063A
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.
| Study group | Role | What they receive |
|---|---|---|
| Water as a vehicle of amoxicillin | Active comparator | Amoxicillin 500 mg was dissolved in 10 ml water and orally administered in a fasting state. Receives: 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. Receives: Drug: Human milk-dissolved amoxicillin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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).
Measured: 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
Measured: 0, 0.25, 0.5, 1, 1.5, 3, 4 and 8 hours after dosing
Tmax
Time to reach Cmax after administration
Measured: 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
Elimination rate constant (Kel) was estimated from the terminal log-linear phase of the concentration-time profiles. Then, elimination half-life was calculated as follows: ln2/Kel.
Measured: Data points were taken at 0, 0.25, 0.5, 1, 1.5, 3, 4 and 8 hours after dosing.
Clearance/F
The log-trapezoidal method was used to calculate AUC last (AUC from time 0 to 8 h), and AUC∞ was estimated using an elimination rate constant (Kel) of the terminal log-linear phase (β phase) of the concentration time profile extrapolating to time infinity. Then, CL/F was derived from Dose/AUC∞. F is bioavailability, which cannot be determined in this study, and therefore, we estimate CL/F, but not CL itself.
Measured: Data points were taken at 0, 0.25, 0.5, 1, 1.5, 3, 4 and 8 hours after dosing.
Volume of Distribution/F
It was estimated from (Clearance/F)/Kel. Elimination rate constant (Kel) was estimated from the terminal log-linear phase of the concentration-time profiles. Then, elimination half-life was calculated as follows: ln2/Kel.
Measured: Data points were taken at 0, 0.25, 0.5, 1, 1.5, 3, 4 and 8 hours after dosing.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2011 (estimated)
- Study startJun 2011
- Primary completionSep 2013
- Study completionOct 2013
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.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by The Hospital for Sick ChildrenThe 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Hospital for Sick Children
- Sponsor type
- University, hospital or other
- Collaborators
- World Health Organization
- Responsible party
- Principal investigator, Shinya Ito, The Hospital for Sick Children
- Investigators
- Shinya Ito, MD, Principal investigator, The Hospital for Sick Children
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01435824
- Sponsor's protocol ID
- 1000021187
- Status last verified
- Jan 2020
- First submitted
- 15 Sep 2011
- Last updated
- 21 Jan 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bioavailability of Amoxicillin Dissolved in Human Milk: An Adult Volunteer Study as a First Step Towards Defining Drug Doses for Infants
- ClinicalTrials.gov ID
- NCT01435824
- Acronym / sponsor ID
- 1000021187
- Conditions
- Healthy
- Keywords
- healthy adult volunteers, comparative bioavailability, amoxicillin, breast milk, Amoxicillin Bioavailability in breast milk
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- The Hospital for Sick ChildrenUniversity, hospital or other
- Collaborators
- World Health Organization
- Study start
- Jun 2011
- Primary completion
- Sep 2013 (actual)
- Study completion
- Oct 2013 (actual)
- First posted
- 19 Sep 2011 (estimated)
- Results
- Posted 21 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
As recommended by the Expert Committee on Selection and Use of Essential Medicines, WHO (http://www.who.int/selection_medicines/committees/en/index.html), oral solid formulations are the preferred forms of medicines for children, especially in developing countries, because of relatively inexpensive and less complicated manufacturing, transporting and storage processes. Whereas solid dosage forms are advantageous in these pharmaceutical logistics, administering solid formulations to infants and children is a challenging issue. Dissolving medicines in water may be acceptable, but safety of drinking water for infants in developing countries and water solubility of the drug itself are major concerns. These challenges are exemplified in the treatment of infectious diseases and diarrhea in infants. Commonly used drugs for infants in low income settings include antibiotics such as amoxicillin. Expert sources have suggested that drug administration in breast milk may be effective. However, little data is currently available to support the recommendation to administer medications dissolved in breast milk to infants.
The second stage of the project will use the information obtained from the first stage, combined with pre-existing data, to define a rational dosing schedule of the target drug dissolved in human milk for young children, using population PK modeling and simulation. This is a study in silico.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Water as a vehicle of amoxicillin | Active comparator | Drug: Water-dissolved amoxicillinAmoxicillin 500 mg was dissolved in 10 ml water and orally administered in a fasting state. |
| Human milk as a vehicle of amoxicillin | Experimental | Drug: Human milk-dissolved amoxicillinAmoxicillin 500 mg was dissolved in 10 ml human milk and orally administered in a fasting state. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (17 listed)
- 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:
- Participation in another clinical trial or receiving an investigational drug within 30 days of the study commencement or during the study
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 |
|---|---|---|
| Human milk-dissolved amoxicillinAlso: Novamoxin 250 from Novopharm, Toronto, Canada: Lot#35422063A, Frozen human milk was obtained from the Mother's Milk Bank of Ohio (USA)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. | Drug | Human milk as a vehicle of amoxicillin |
| Water-dissolved amoxicillinAlso: Novamoxin 250 from Novopharm, Toronto, Canada: Lot#35422063AAn 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. | Drug | Water as a vehicle of amoxicillin |
Primary outcome
Area Under the Curve to Time Infinity (AUC to Time Infinity)
Time frame: Baseline, 0.25, 0.5, 1, 1.5, 3, 4 and 8 hours after dosing
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.
Area Under the Curve to 8h (AUC Last)
Time frame: Baseline, 0.25, 0.5, 1, 1.5, 3, 4 and 8 hours after dosing
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).
Cmax
Time frame: 0, 0.25, 0.5, 1, 1.5, 3, 4 and 8 hours after dosing
A maximum plasma concentration of amoxicillin within the time frame of a dosing
Tmax
Time frame: Data points were taken at 0, 0.25, 0.5, 1, 1.5, 3, 4 and 8 hours after dosing.
Time to reach Cmax after administration
3 secondary outcomes
Elimination Half-life
Time frame: Data points were taken at 0, 0.25, 0.5, 1, 1.5, 3, 4 and 8 hours after dosing.
Clearance/F
Time frame: Data points were taken at 0, 0.25, 0.5, 1, 1.5, 3, 4 and 8 hours after dosing.
Volume of Distribution/F
Time frame: Data points were taken at 0, 0.25, 0.5, 1, 1.5, 3, 4 and 8 hours after dosing.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jan 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Link to published study resultsLink provided by the sponsor.
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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.
Shinya Ito, MD principal investigator
The Hospital for Sick Children
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 Human milk-dissolved amoxicillin and Water-dissolved amoxicillin in people with Healthy, run by The Hospital for Sick Children at 1 site in Canada.
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 11 inclusion and 17 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 21 Jan 2020. 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 Canada. 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 21 Jan 2020). 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?
Area Under the Curve to Time Infinity (AUC to Time Infinity) (time frame: Baseline, 0.25, 0.5, 1, 1.5, 3, 4 and 8 hours after dosing). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 21 Jan 2020.