E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Memory loss, attention deficit |
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E.1.1.1 | Medical condition in easily understood language |
Memory loss, attention deficit |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Psychological processes [F02] |
MedDRA Classification |
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 |
Provide proof-of-concept for the hypothesis that guanfacine diminishes cognitive side-effects in ER+ BC patients treated with adjuvant hormonal therapy. |
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E.2.2 | Secondary objectives of the trial |
Provide data for power calculations in later studies. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• treated with adjuvant tamoxifen therapy for ER receptor-positive Breast Cancer • on tamoxifen treatment for 3-18 months, 20 mg stable dosing for at least a month • postmenopausal • subjective complaints of cognitive side effects • weight between 50 and 90 kg • 20 ≤ BMI ≤ 27 • fluent in Dutch • normal (or corrected-to-normal) vision • normal dexterity
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E.4 | Principal exclusion criteria |
• prior exposure to chemotherapy • diagnosis of prior or existing cardiovascular, neurological or psychiatric disorder that may influence sensitivity to guanfacine or study endpoint(s) • contraindications for guanfacine (hypotension, bradycardia, syncope, extended QT interval, cardiac conduction abnormalities, AV block, sinus node dysfunction) • (prior) diagnosis of ADHD • use of clonidine or other anti-hypertensive agents • use of drugs with a strong influence on CYP2D6, CYP3A4/5 (e.g., ketoconazole, carbamazepine) • use of SSRIs and other antidepressants
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E.5 End points |
E.5.1 | Primary end point(s) |
Difference in cognitive functions between placebo and guanfacine condition. Cognitive functions are assessed by standardized neuropsychological tasks and include executive functions, attention, memory, and processing speed. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Difference in affect between placebo and guanfacine condition. Affect is measured by a standardized questionnaire (POMS). Difference in physical side-effects between placebo and guanfacine condition. Side-effects recorded include those reported for tamoxifen and guanfacine. The most commonly reported side effects for tamoxifen (hot flushes, vaginal bleeding and secretions, pruritus vulvae) and guanfacine (sedation, headache, abdominal pains, signs and symptoms related to changes in blood pressure) are explicitly asked about during a weekly structured telephone interview. Patients will be asked to report any remaining side-effects as well.
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
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 | No |
E.8.1.6 | Cross over | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 9 |
E.8.9.1 | In the Member State concerned days | 0 |