E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
healthy volunteers (Venous Thromboembolism) |
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E.1.1.1 | Medical condition in easily understood language |
healthy volunteers (Blood clots during breast feeding) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10049909 |
E.1.2 | Term | Venous thromboembolism prophylaxis |
E.1.2 | System Organ Class | 100000004865 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine if apixaban and rivaroxaban are excreted in breastmilk following single dose oral administration to breastfeeding mothers. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the concentration-time profiles of apixaban and rivaroxaban in the plasma and breastmilk of breastfeeding mothers, and therefore to establish the potential exposure of breastfed infants to apixaban and rivaroxaban |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject is informed and given ample time and opportunity to think about his/her participation and has provided written informed consent for participation in the study before any study specific procedures take place. 2. Subject is considered reliable and capable of adhering to applicable protocol requirements, including the study drug being administered orally and visit schedule according to the judgement of the Investigator. 3. Women are aged ≥18 years. 4. At least 6 weeks postpartum when enter the study. 5. Decision has been confirmed by the woman to stop breastfeeding their baby soon. 6. Negative pregnancy test. 7. Good physical and mental health, in the opinion of the Investigator, determined on the basis of medical history and general clinical examination at Screening. 8. Women have clinical laboratory test results within the reference ranges of the testing laboratory: normal renal function test – results of the serum creatinine <90 micro mol/L. Normal liver function tests – results of the serum ALT </= 40 IU/L. 9. Women are not taking any medication interacting with apixaban or rivaroxaban, as listed in table 6.4 and 6.5. 10. Women are available to attend scheduled visits at clinical unit and permit the clinic staffs visit home to collect blood and milk samples. 11. Women agree to the study restrictions
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E.4 | Principal exclusion criteria |
1. Women who are unable to provide written informed consent. 2. LMWH thromboprophylaxis is indicated. 3. Increased risk of bleeding for any reason. 4. Known contra-indications to apixaban or rivaroxaban. 5. On-going treatment with aspirin, NSAIDs or other drugs that affect haemostasis. 6. Treatment with oral ketoconazole or itraconazole, medicines to treat fungal infections. 7. Patients who have received an artificial heart valve, have had a heart attack or suffer an irregular heartbeat (including taking dronedarone). 8. Known impaired renal function (serum creatinine > 90 micro mol/L). 9. Known abnormal liver function tests (ALT > 40 IU/L). 10. Known hypersensitivity or allergy to apixaban or rivaroxaban. 11. Use of other investigational study drugs within 30 days prior to study entry. 12. Women who are pregnant or of childbearing potential who refuse to use an acceptable effective form of contraception throughout the study. 13. Women who will not participate in study visits within a suitable distance from King’s College Hospital NHS Foundation Trust, as judged by the investigator.
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E.5 End points |
E.5.1 | Primary end point(s) |
Apixaban and its metabolites in plasma and breast milk will be measured at 0, 3-4, 7, 12, 14, 16, 24 hours after swallowing two 5mg capsules of apixaban (1 capsule 12 hours apart). Rivaroxaban in plasma and breast milk will be measured at 0, 2-3, 6, 10, 12, 24 hours after swallowing one 20mg tablet of rivaroxaban. Milk sampling from both breasts will be done at each time point.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Apixaban and its metabolites in plasma and breast milk will be measured at 0, 3-4, 7, 12, 14, 16, 24 hours after swallowing two 5mg capsules of apixaban (1 capsule 12 hours apart). Rivaroxaban in plasma and breast milk will be measured at 0, 2-3, 6, 10, 12, 24 hours after swallowing one 20mg tablet of rivaroxaban. Milk sampling from both breasts will be done at each time point.
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E.5.2 | Secondary end point(s) |
The following PK parameters for apixaban and rivaroxaban in milk and plasma will be the endpoints: Area under the concentration-time curve (AUC) from zero to the time of the last quantifiable concentration (AUC(0-t)); AUC from zero to the time of 24 hours (AUC(0-24)). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 31 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 31 |