E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Adult Growth Hormone Deficiency |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10056438 |
E.1.2 | Term | Growth hormone deficiency |
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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 |
Main objectives:
To explore the safety, toleration and humoral response of PHA-794428 after multiple weekly injections in AGHD patients.
To explore the dose response relationship of PHA-794428 after multiple weekly subcutaneous injections in AGHD patients.
To explore the PK/PD relationships with PHA-794428 after single and multiple injections.
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male and female patients between the ages of 25-60 yrs with severe AGHD as defined by GRS Guidelines (3). Patients may be included if they had idiopathic severe GHD in childhood, which is still present on re-testing, or if they have isolated GHD with evidence of hypothalamic/pituitary pathology.
2. Hypopituitary patients must be on adequate hormone replacement therapy for at least 6 months. Patients must be demonstrated to have adequate cortisol reserve or be on adequate glucocorticoid replacement therapy.
3. GH treated patients will have a minimum of 3 weeks washout (and not longer than 4 weeks) prior to dosing.
4. Written informed consent.
5. Patient must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other program procedures.
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E.4 | Principal exclusion criteria |
1. AGHD patients with uncontrolled pituitary tumor growth. Patients with pituitary tumors must have demonstrated stable neuroimaging within 12 months of the screening visit.
2. Tumors within 3 mm of the optic chiasm. Patients with residual suprasellar disease, must be scanned within 3 months of the screening visit.
3. Serum ALT and/or AST ≥ 1.5 times the upper limit of normal range (ULN), or clinically significant hepatic disease.
4. Patients with diabetes mellitus. Impaired glucose tolerance without drug treatment is permissible.
5. Patients who drink more than 28 units per week (1 unit = 1/2 pint of beer (285mL) or 25mL of spirits or one glass (125mL) of wine).
6. Patients with a history of clinically significant allergies, especially drug hypersensitivity.
7. Patients who have evidence of drug or substance abuse.
8. Patients who have donated blood or blood products during the previous two months or intend to donate blood or blood products during the study or for two months following the completion of the study.
9. Patients who have a positive screening for HIV, Hepatitis B surface antigen (HBsAg) or Hepatitis B core antibody (HBcAb) or anti-hepatitis C virus serology (as determined by a multi-antigen EIA).
10. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration, or may interfere with the interpretation of trial results and, in the judgment of the investigator, would make the patient inappropriate for entry into this trial (e.g.active malignant disease, morbid obesity BMI ³40).
11. Pregnant or lactating women.
12. Female of child-bearing potential who is unwilling or unable to use adequate contraception to prevent pregnancy during the study.
13. Concomitant therapy with other investigational drugs or participation in another clinical trial in the last 6 months.
14. Requirement to use medication during the study that might interfere with the evaluation of the study drug. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Responder status at visits 9 (week 4) and 14 (week 7), where responder is defined as a patient who has achieved an IGF-1 level above the mid-point of the age-related normal range. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
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 | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Third party open to study site pharmacist |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 42 |
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 | Information not present in EudraCT |
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 |
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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 | 11 |
E.8.9.1 | In the Member State concerned days | |
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 | 11 |