| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Major Depressive Disorder |
|
| E.1.1.1 | Medical condition in easily understood language |
| Major Depressive Disorder |
|
| E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 16.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10025463 |
| E.1.2 | Term | Major depressive disorder, single episode |
| E.1.2 | System Organ Class | 100000004873 |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 16.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10025454 |
| E.1.2 | Term | Major depressive disorder, recurrent episode |
| E.1.2 | System Organ Class | 100000004873 |
|
| 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 |
| The objectives of this study are to evaluate the efficacy, safety, and tolerability of cariprazine adjunctive to ADT in patients with major depressive disorder who have an inadequate response to ADT. |
|
| E.2.2 | Secondary objectives of the trial |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
To be eligible to participate in the study, patients must meet the
following criteria:
1. Written informed consent, signed or thumbprinted (only if allowed by
local
regulations), obtained from the patient before the initiation of any
study-specific
procedures
2. Male or female outpatients 18 to 65 years of age, inclusive
3. Currently meet the DSM-IV-TR criteria for MDD without psychotic
features based
on the Structured Clinical Interview for Diagnostic Statistic Manual of
Mental Health
Disorders, Fourth Edition (SCID), with a current major depressive
episode of at least
8 weeks and not exceeding 24 months in duration at Visit 1
4. Ongoing inadequate response to protocol allowed ADT (bupropion,
citalopram,
desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline,
venlafaxine, or
vilazodone) administered at adequate dose and duration in accordance
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with the
respective package insert, documented in the Antidepressant Treatment
History Form
(ATHF) with a resistance rating of ≥ 3 and a global confidence score of ≥
3
5. Montgomery-Asberg Depression Rating Scale (MADRS) total score ≥
22 at both
Screening (Visit 1) and Baseline (Visit 2)
6. Normal physical examination findings, clinical laboratory results, and
electrocardiogram (ECG) results from Screening (Visit 1) or abnormal
findings
judged not clinically significant by the PI and documented as such in the
eCRF
7. Body mass index between 18 and 40, inclusive
8. If female of child bearing potential, have a negative serum β-human
chorionic
gonadotropin (β-hCG]) pregnancy test |
|
| E.4 | Principal exclusion criteria |
Psychiatric Criteria:
1. Principal DSM-IV-TR–based diagnosis of an axis I disorder, other than
MDD, or
any axis I disorder other than MDD that was the primary focus of
treatment within
6 months before Visit 1 (secondary diagnoses of comorbid generalized
anxiety
disorder, social anxiety disorder, or specific phobias are acceptable)
2. History of meeting DSM-IV-TR criteria for:
a. Any depressive episode with psychotic or catatonic features
b. Any manic, hypomanic or mixed episode, including bipolar disorder
and
substance-induced (eg, antidepressant-induced) manic, hypomanic or
mixed
episode
c. Schizophrenia, schizoaffective, or other psychotic disorder
d. Panic disorder, with or without agoraphobia
e. Obsessive-Compulsive disorder
f. Bulimia or Anorexia Nervosa
g. Dementia, amnesic, or other cognitive disorder
h. Mental retardation
3. Meeting full DSM-IV-TR criteria for MDD "with seasonal pattern" AND
the
patient's season of remission would occur during the study.
4. DSM-IV-TR–based diagnosis of borderline or antisocial personality
disorder or other
axis II disorder of sufficient severity to interfere with participation in
this study
5. History of meeting DSM-IV-TR criteria for alcohol or substance abuse
or dependence
(other than nicotine or caffeine) within the 6 months before Visit 1
6. Positive result on blood alcohol test or for any prohibited medication
on the urine
drug screen with the following stipulations:
○ Patients with a positive urine drug screen for cannabinoids,
barbiturates, opiates,
amphetamines, or benzodiazepines may be allowed in the study provided
that the
drug was used for a legitimate medical purpose and the use of such
products can
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be discontinued (documented by a negative repeat test) before
participation
beyond screening
○ Medically appropriate episodic use (up to 3 days) of narcotic analgesics
for acute
medical indications is allowed
○ Discussion with Medical Monitor is recommended in any potential
exception
listed above
○ Positive results for methadone, phencyclidine, and cocaine are
exclusionary with
no exceptions
7. Suicide risk, as determined by meeting any of the following criteria:
○ A suicide attempt within the past year
○ Significant risk, as judged by the PI, based on the psychiatric interview
or
information collected in the Columbia–Suicide Severity Rating Scale (CSSRS)
at
Visit 1 or Visit 2
○ MADRS Item 10 score ≥ 5 at Visit 1 or Visit 2
8. At imminent risk of injuring self or others or causing significant
damage to property,
as judged by the PI
9. Requires hospitalization
Treatment-Related Criteria:
10. Treatment refractory depression as defined by:
○ Failure to respond (< 50% reduction in depressive symptoms) to ≥ 3
ADTs
given at adequate dose (as defined by the ADT package insert) and
duration of
> 6 weeks during the present episode
○ History of inadequate response to ECT, a monoamine oxidase inhibitor,
or
adjunctive treatment with an antipsychotic
11. Having a history of treatment with clozapine or any depot
antipsychotic (exception:
episodic use of clozapine at doses ≤ 150 mg/day for the treatment of
insomnia)
12. Having received any antipsychotic, anticonvulsant/mood stabilizer,
anxiolytic,
benzodiazepine, or other ADT augmentation agent (eg, T3 [except as
treatment for
thyroid condition], 2nd antidepressant, etc.) within 1 week or 5 half lives
of the
medication, whichever is longer, prior to Visit 2; however, 4 weeks for
T3, 2 weeks is
required for monoamine oxidase inhibitors, lithium must be tapered and
discontinued
over a minimum of two weeks followed by a 1- week washout, and safe
withdrawal
from benzodiazepine treatment is left to the discretion of the principal
investigator
13. History of electroconvulsive therapy (ECT), vagus nerve stimulation,
transcranial
magnetic stimulation, or any experimental central nervous system
treatment during
the current episode or in the 6 months before Visit 1 (whichever is
longer)
14. Requiring concomitant treatment with any of the prohibited
medications,
supplements, or herbal products listed in Appendix III, including any
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psychotropic
drug or any drug with psychotropic activity or with a potentially
psychotropic
component, except for the following:
○ Eszopiclone, zolpidem, zolpidem extended-release, zopiclone or
zaleplon for
insomnia may be continued provided the medication has been used in a
consistent
manner for 4 weeks prior to enrollment. Following randomization these
medications may be introduced as specified in the concomitant
medication
section.
15. Requiring concomitant treatment with strong CYP3A4 inhibitors or
inducers
16. Prior participation in any investigational study of RGH-188 or
cariprazine
E.5 |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The Montgomery-Åsberg Depression Rating Scale
The primary efficacy parameter will be the change from baseline in MADRS total score |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
The Sheehan Disability Scale.
The secondary efficacy parameter will be the change from baseline in SDS score. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | No |
| 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) | 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 | 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.8.2.4 | Number of treatment arms in the trial | 3 |
| 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 | 8 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 50 |
| 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 |
|
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
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