| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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| E.1.1.1 | Medical condition in easily understood language |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 19.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10003553 |
| E.1.2 | Term | Asthma |
| E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
|
| 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 compare the pharmacokinetics of subcutaneous mepolizumab following a single dose of the. liquid drug product in safety syringe with the lyophilized drug product
To compare the pharmacokinetics of subcutaneous mepolizumab following a single dose of the liquid drug product in autoinjector with the lyophilized drug product. |
|
| E.2.2 | Secondary objectives of the trial |
- To assess additional pharmacokinetic parameters following mepolizumab subcutaneous administration of the
liquid drug product in autoinjector or the liquid drug product in safety syringe in comparison with the lyophilized drug product, as data permit.
- To assess the safety and tolerability of mepolizumab following a single SC dose of the liquid drug product in autoinjector or the liquid drug product in safety syringe in comparison with the lyophilised drug product
- To assess the immunogenicity of mepolizumab following a single SC dose of the liquid drug product in
autoinjector or the liquid drug product in safety syringe in comparison with the lyophilised drug product |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
A subject will be eligible for inclusion in this study only if all of the following criteria are met:
AGE:
1. 18 years of age and over at the time of signing the informed consent.
TYPE OF SUBJECT AND DIAGNOSIS INCLUDING DISEASE SEVERITY
Healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, vital signs, laboratory tests, and cardiac monitoring. A subjectwith a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or
exclusion criteria, outside the reference range for the population being studied may be included only if the investigator agrees and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures or ability to interpret study results.
WEIGHT
3. Body weight ≥ 50 kg and body mass index (BMI) within the range 19.0-30kg/m2 (inclusive)
SEX
4. Male or Female.
5. A female subject is eligible to participate if she is not pregnant (as confirmed by a negative human chorionic gonadotrophin (hCG) test), not lactating, and at least one of the following conditions applies:
a. Non-reproductive potential defined as:
- Pre-menopausal females with one of the following:
- Documented tubal ligation
- Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion
- Hysterectomy
- Documented Bilateral Oophorectomy
- Post- menopausal females- refer to Appendix 5 for definition
b. Subject is of reproductive potential and agrees to follow one of the options listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) (Appendix 5) from 30 days prior to the first dose of study medication and until 16 weeks after the administration of the single dose of study medication.
INFORMED CONSENT
6. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in the protocol. The subject must be able to understand and communicate in the native language of the site, e.g. German in German sites. |
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| E.4 | Principal exclusion criteria |
A subject will not be eligible for inclusion in this study if any of the following criteria apply:
CONCURRENT CONDITIONS/MEDICAL HISTORY (INCLUDES LIVER FUNCTION AND QTc INTERVAL)
1. ALT >1.5 xULN
2. Bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
3. Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
4. QTcF > 450 msec
5. Any clinically relevant abnormality identified at the screening medical assessment (physical examination/medical history), clinical laboratory tests, or 12-lead ECG.
CONCOMITANT MEDICATIONS
6. Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John’s Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) before the first dose of study medication and until study completion, unless in the opinion of the
investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
RELEVANT HABITS
7. History of regular alcohol consumption within 6 months of the study defined as:
8. An average weekly intake of >14 units for females and >21 units for males. One unit is equivalent to 8 g of alcohol: a half-pint (~240 ml) of beer, 1 glass (125 ml) of wine or 1 (25 ml) measure of spirits.
9. Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening. Limit of >500 ng/mL.
10. Involved in any activities likely to result in any significant decrease or increase in body weight during the study period (e.g. ‘crash’ dieting, bodybuilding).
CONTRAINDICATIONS
11. History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.
DIAGNOSTIC ASSESSMENTS AND OTHER CRITERIA
12. Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.
13. A positive test for HIV antibody.
14. Subjects with known, pre-existing helminthes infestation within 6 months prior to Day 1.
15. Where participation in the study would result in donation of blood or blood products in excess of 500 mL within 3 months.
16. The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
17. Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
18. A positive pre-study drug/alcohol screen.
19. A vulnerable subject. Defined as individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate.
20. Subjects who work for the Sponsor, CRO, or one of the study centres. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| - Mepolizumab PK parameters: Cmax, AUC(0-t) and AUC(0-∞). |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Day 1, 24h (Day 2), 48h (Day 3) and on Days 4, 5, 6, 7, 8, 9, 10, 15, 22, 29, 43, 57 and 85. |
|
| E.5.2 | Secondary end point(s) |
- tmax, CL/F, Vd/F, λz, t ½, tlast, %AUCex.
- Adverse events (AEs), serious adverse events (SAEs), including systemic
reactions and injection site reactions.
- Haematology and Clinical Chemistry
- Vital signs
- 12-lead ECG
- Frequency of positive antimepolizumab binding antibodies and neutralizing antibodies |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Day 1, 24h (Day 2), 48h (Day 3) and on Days 4, 5, 6, 7, 8, 9, 10, 15, 22, 29, 43, 57 and 85. |
|
| 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 | Yes |
| 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) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| 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) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| 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 | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 2 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Germany |
| United Kingdom |
| United States |
|
| 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 | |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
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