E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Generalized Anxiety Disorder |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10018075 |
E.1.2 | Term | Generalised anxiety disorder |
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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 evaluate the efficacy of 5 mg Lu AA21004 QD versus placebo after 8 weeks of treatment in subjects with GAD. |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the efficacy of 5 mg Lu AA21004 QD compared with placebo during the 8-week, double-blind treatment. • To evaluate the proportion of subjects who respond to Lu AA21004 treatment compared with placebo after 8 weeks of treatment. • To evaluate the proportion of subjects who are in remission after 8 weeks of treatment with Lu AA21004 compared with placebo. • To evaluate the effect of Lu AA21004 on global clinician-rated assessments. • To evaluate the effect of Lu AA21004 on patient-rated assessments of anxiety, quality of life, and disability. • To evaluate the effects of Lu AA21004 on health care resource utilization. • To evaluate the population pharmacokinetics of Lu AA21004 and its metabolites Lu AA34443 and Lu AA39835. • To evaluate the safety and tolerability of 5 mg Lu AA21004 QD compared with placebo during the course of treatment.
Exploratory Objective: • To assess the treatment effect (Lu AA21004 or placebo) on suicidal ideation and behavior. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subject eligibility is determined based on the following criteria: 1. Subjects who suffer from a primary diagnosis of GAD according to DSM-IV-TR criteria (classification code 300.02). 2. Subjects with a Hamilton Anxiety Scale (HAM-A) total score ≥20 at Screening and Baseline. 3. Subjects with a HAM-A score ≥2 on both Item 1 (anxious mood) and Item 2 (tension) at Screening and Baseline. 4. Subjects with a Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≤16 at Screening and Baseline. 5. Male or female subjects, aged between 18 years or older. 6. The subject is capable of understanding and complying with protocol requirements. 7. Male subjects, or female subjects of childbearing potential, who are sexually active agree to use adequate contraception from Screening throughout the duration of the study and for 1 month after the last dose of study medication. Women not of child bearing potential are defined as those who have been surgically sterilized (documented hysterectomy, bilateral oophorectomy, or tubal ligation) or who are postmenopausal (defined as greater than or equal to 48 years of age and at least 2 years since menses). [Acceptable methods of contraception are defined in the Contraception and Pregnancy Avoidance Procedure Section of the protocol.] 8. Subjects who are able to understand and sign the informed consent form prior to undergoing any study-related procedures. |
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E.4 | Principal exclusion criteria |
Subjects who meet any of the following criteria will not qualify for entry into the study: 1. The subject has received any investigational compound <30 days before Screening or 5 half-lives prior to Screening. 2. The subject has received Lu AA21004 in a previous clinical study or as a therapeutic agent. 3. The subject is a study site employee, or is an immediate family member (ie, spouse, parent, child, or sibling) of a study site employee involved in conduct of this study. 4. The subject has 1 or more of the following: a) Any current psychiatric disorder other than GAD as defined in the DSM-IV-TR (as assessed by the Mini International Neuropsychiatric Interview [MINI]). b) Current or past history of: manic or hypomanic episode, schizophrenia or any other psychotic disorder, including major depression with psychotic features, mental retardation, organic mental disorders, or mental disorders due to a general medical condition as defined in the DSM-IV-TR. c) Any substance disorder (except nicotine and caffeine) within the previous 6 months as defined in the DSM-IV-TR. (Subject must have a negative urine drug screen prior to Baseline). d) Presence or history of a clinically significant neurological disorder (including epilepsy). e) Neurodegenerative disorder (Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, Huntington disease, etc). f) Any Axis II disorder that might compromise the study. 5. The subject is required to take excluded medications or it is anticipated that the subject will require treatment with at least 1 of the disallowed concomitant medications during the study. (Please refer to Section 7.3 Excluded Medications.) 6. If female, the subject is pregnant or lactating. 7. The subject has a significant risk of suicide according to the investigator’s opinion or has a score ≥5 on item 10 (suicidal thoughts) of the MADRS or has made a suicide attempt in the previous 6 months. 8. The subject has previously failed to respond to adequate treatment with selective serotonin reuptake inhibitors (SSRIs) and/or serotonin norepinephrine reuptake inhibitors (SNRIs). 9. The subject has received electroconvulsive therapy within 6 months prior to Screening. 10. The subject is currently receiving formal cognitive or behavioral therapy, systematic psychotherapy, or plans to initiate such therapy during the study. 11. The subject has a clinically significant unstable illness, for example, hepatic impairment or renal insufficiency, or a cardiovascular, pulmonary, gastrointestinal, endocrine, neurological, rheumatologic, immunologic, infectious, skin and subcutaneous tissue disorders, or metabolic disturbance. 12. The subject has an alanine aminotransferase, aspartate aminotransferase or bilirubin level >1.5 times the upper limits of normal (×ULN). 13. The subject has a serum creatinine of >1.5 ×ULN. 14. The subject has a previous history of cancer that had been in remission for less than 5 years prior to the first dose of study medication. This criterion does not include those subjects with basal cell or stage I squamous cell carcinoma of the skin. 15. The subject has clinically significant abnormal vital signs as determined by the investigator. 16. The subject has 1 or more laboratory values outside the normal range, based on the blood or urine samples taken at Screening, that are considered by the investigator to be clinically significant. 17. The subject has thyroid stimulating hormone value outside the normal range at the Screening Visit and is deemed clinically significant by the investigator. 18. The subject has an abnormal electrocardiogram (ECG) as determined by the central reader and confirmed as clinically significant by the investigator. 19. The subject has a disease or takes medication that, in the opinion of the investigator, could interfere with the assessments of safety, tolerability, or efficacy. 20. The subject, in the opinion of the investigator, is unlikely to comply with the clinical study protocol or is unsuitable for any reason. 21. The subject has previously participated in this study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint for this study is the least squares (LS) mean change from Baseline in the 14-item HAM-A total score after 8 weeks of treatment.
Secondary Endpoints Efficacy: Secondary efficacy endpoints for this study are: • LS mean change from Baseline in HAM-A total score at each week assessed. • Response rates at Week 8, with response defined as a ≥50% decrease in the HAM-A total score from Baseline. • Remission rates at Week 8, with remission defined as a HAM-A total score ≤7. • LS mean change from Baseline in CGI-I, CGI-S, and Hospital Anxiety and Depression Scale (HAD) at all study visits where rated.
Pharmacoeconomic Measures: The following will be evaluated: • Sheehan Disability Scale (SDS). • Medical Outcomes Study (MOS) 36-Item Short-Form Health Survey (SF-36®). • Health care resource utilization as assessed by the Health Economic Assessment Questionnaire (HEA).
Pharmacokinetic Endpoints: Individual exposure parameters of Lu AA21004 and its metabolites Lu AA34443 and Lu AA39835 (eg, area under the plasma concentration-time curve from time 0 to time tau (AUC[0-tau]), average observed plasma concentration (Cavg), and maximum observed plasma concentration (Cmax)) will be estimated and their correlation with relevant pharmacodynamic parameters (effect and tolerability/safety) will be explored.
Exploratory Endpoints The Columbia-Suicide Severity Rating Scale (C-SSRS) will be utilized as an exploratory assessment. |
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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 | Yes |
E.6.5 | Efficacy | Yes |
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 | Yes |
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 | 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 | 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.8.3 |
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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 36 |
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 | 15 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 18 |
E.8.9.2 | In all countries concerned by the trial days | 0 |