Major Depressive Disorder
Conditions
Keywords
MDD, Depression, Mecamylamine, Add-on Therapy, Major Depressive Disorder
Brief summary
Depressed patients will receive 6 weeks of citaloprma (20-40mg) therapy. Subjects who have an inadequate response (partial or non-responder) will be randomized to receive either mecamylamine (5-10mg) or placebo added to their citalopram for a further 8 weeks.
Detailed description
This is a double blind, randomized, placebo controlled, parallel group, flexible dose titration, add-on study. Male or female subjects aged 18-70 years suffering from Major Depressive Disorder according to DSM-IV, with a HAMD-17 score greater than 21 and a CGI-Severity of Illness score greater or equal to 4, will be started on open labeled citalopram treatment. The dose of citalopram may be increased form 20mg to 40mg over a six week period, depending on investigator assessment of tolerability and efficacy. At the end of this treatment, subjects with a HAMD-17 score greater or equal to 14 and a CGI-Severity of Illness score greater or equal to 4 will be considered as partial or non-responders and will be entered into the double blind phase of the study. Subjects will be randomized to either mecamylamine or placebo for a further 8 weeks. Citalopram medication will remain constant while mecamylamine (or placebo) can be increased from 5.0 to 7.5 to 10.0mg based on investigator assessment of tolerability and efficacy. Plasma samples for citalopram assay will be collected at the start and end of the double blind phase to exclude any mecamylamine effect being due to a drug:drug interaction. Approximately 500 subjects will be entered into the open-label phase of the study and approximately 160 into the double blind phase. The study will be conducted in India and the USA.
Interventions
DRUGMecamylamine
2.5mg mecamylamine Hcl, tablet form taken twice a day (total of 5.0mg). For 7.5 mg dose group, 2 tablets taken morning, one tablet evening. At 10.0mg, 2 tablets taken twice daily.
Sponsors
Targacept Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
(A) Open Phase * Male or female subjects aged 18-70 years. * Diagnosis of major depressive disorder (MDD) according to DSM-IV and confirmed via MINI diagnostic scale. * Able to give written informed consent. * HAMD-17 score greater than 21. * CGI-Severity of Illness score greater than or equal to 4. * No clinically significant abnormality on physical examination, vital signs, ECG or laboratory tests (biochemical, hematological, urinary) at screening. * Women of child bearing potential with a negative urine pregnancy test and willing to use acceptable methods of contraception. (B)Double Blind Phase: * Subjects still to meet DSM-IV criteria for MDD. * Subjects continue to meet all of the inclusion and
Exclusion criteria
. * HAMD-17 score greater than or equal to 14. * CGI severity of illness score greater than or equal to 4. * Women of child bearing potential with a negative urine pregnancy test and willing to use acceptable methods of contraception.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| HAMD-17 group mean change from baseline to endpoint and/or the proportion of subjects considered to be full responders or in remission with a HAMD-17 score less than or equal to 7 at the end of treatment. | 8 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Montgomery Asbery depression rating sclae, Clinical Global Impression Scale - Severity, Clinical Global Impression Sacle - Change, Sheehan irritability scale, Sheehan disability scale | 8 weeks |
| Blood biochemistry, urnie analysis, blood pressure, heart rate, ECG | 8 weeks |
| Citalopram plasma bloods at week 6 and 14. | 8 weeks |
Outcome results
None listed