nemifitide-ditriflutate and Depressive-Disorder--Major

Nemifitide is a peptide under development by Innapharma for the potential treatment of depression. By June 2001, the first phase II trial of nemifitide in moderate to severely depressed individuals had been completed and in February 2003, Innapharma anticipated that phase III trials would commence later that year.

Topics: Animals; Clinical Trials as Topic; Depressive Disorder, Major; Drugs, Investigational; Humans; Oligopeptides; Technology, Pharmaceutical

Clinical data were evaluated from an open-label, single-center, pilot study in patients with chronic refractory depression. The primary efficacy criterion was the change from baseline using the Montgomery-Asberg Depression Rating Scale. The secondary efficacy criteria were the 17-item Hamilton Depression Rating Scale and the Clinical Global Impression-Improvement scale. Response to treatment (40-240 mg once per day by subcutaneous injection for 10-20 doses) was defined as more than 50% improvement in the Montgomery-Asberg Depression Rating Scale from baseline or Clinical Global Impression-Improvement < or =2 and lasting for at least two sequential weeks. Patients with a sustained response at the end point in the acute main treatment phase were enrolled for up to 2 years in a maintenance phase of the study to determine duration of response and to initiate retreatments upon relapse. Of the 25 patients with chronic refractory depression, 11 patients showed a response for Montgomery-Asberg Depression Rating Scale and one responded according to the secondary criterion Hamilton Depression Rating Scale. In seven of the 11 responders to Montgomery-Asberg Depression Rating Scale the effects were sustained for the remainder of the acute phase. Two additional sustained responders identified according to secondary criteria (Hamilton Depression Rating Scale or Clinical Global Impression-Improvement) were also enrolled in the maintenance phase. All nine sustained responders were retreated, as needed, in the maintenance phase of the study, ranging from 71 to 660 days. Mean duration of response following initial treatment and between retreatments was around 2 months. Pharmacokinetic data indicated dose-proportional systemic exposure to the drug.

Topics: Adult; Antidepressive Agents; Depressive Disorder, Major; Dose-Response Relationship, Drug; Drug Resistance; Endpoint Determination; Female; Humans; Injections, Subcutaneous; Male; Middle Aged; Oligopeptides; Pilot Projects; Psychiatric Status Rating Scales

Nemifitide is a novel pentapeptide antidepressant, which appears to be effective in the treatment of major depressive disorder (MDD). In the present study 81 patients with MDD, DSM-IV criteria were randomized following a 1-wk screening period to receive 30 mg/d nemifitide, 45 mg/d nemifitide or placebo in a 6-wk double-blind, multicentre, outpatient efficacy study. Nemifitide or placebo was delivered by subcutaneous injection for 2 wk daily for 5 days (Monday to Friday) in the first 2 wk and patients were followed up for a further 4 wk. The primary efficacy measure was the change from baseline on the Montgomery-Asberg Depression Rating Scale. Secondary measures included the 17-item Hamilton Psychiatric Rating Scale for Depression (HAMD), the CGI severity and improvement scale and the Carroll Self-Rating Scale for Depression. This proof-of-principle study demonstrated a statistically significant superiority of the 45-mg/d dose vs. placebo at the time-point of peak effect (1 wk after the end of treatment). There appeared to be a greater effect with the 45 mg/d nemifitide dose than with 30 mg/d. An additional exploratory analysis by stratification of all patients by severity above and below or equal to the median baseline HAMD score of 22 showed a higher percentage of responders for both doses of nemifitide with statistical separation from placebo for patients with baseline HAMD score of >22 (above the median). There was no significant difference among treatment groups for patients with baseline HAMD score of

Topics: Adult; Analysis of Variance; Antidepressive Agents; Chi-Square Distribution; Depressive Disorder, Major; Diagnostic and Statistical Manual of Mental Disorders; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Evaluation; Female; Humans; Male; Middle Aged; Oligopeptides; Psychometrics; Severity of Illness Index; Sex Factors; Time Factors

Data from two Phase 2 clinical studies with nemifitide, a novel pentapeptide antidepressant, were evaluated. The initial double-blind, placebo-controlled study was performed on outpatients with DSM-IV criteria for major depressive disorder. An open-label extension study enrolled subjects either completing or having been discontinued due to lack of efficacy during the follow-up period of the initial study. In the extension study, both the investigator and the subjects were blinded to the previous treatment in the initial study. No clinically significant side-effects were observed in either study. Twenty-seven subjects have been entered and evaluated in the extension study. Eighteen of these 27 subjects (66.7%) responded to re-treatment in the extension study. Mean duration of effect between re-treatments was 3.3 months. The results of the extension study support investigating a range of doses of nemifitide from 18 to 72 mg/d in future clinical trials. Further studies are planned to determine the most effective nemifitide clinical treatment regimen.

Topics: Adolescent; Adult; Antidepressive Agents; Depressive Disorder, Major; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Oligopeptides; Psychiatric Status Rating Scales; Recurrence

INN 00835 is a synthetic pentapeptide with a potential for rapid onset of action as an antidepressant. Its efficacy was investigated in a pilot study in patients diagnosed with major depression.. Fifty two patients received either active drug - INN 00835 (26 patients) - or placebo (26 patients), subcutaneously at 0.2 mg/kg for 5 consecutive days. The patients were evaluated for an additional 4 weeks after treatment. Efficacy was evaluated by the following psychiatric rating scales: HAMD, MADRS, CSRS, CGI, and VAS. The effect of treatment was also evaluated by using a biochemical marker: changes in blood platelet serotonin (5HT) uptake rates in drug-treated patients compared to those in the placebo group. Plasma concentrations of INN 00835 were measured by LC/MS.. Statistical analysis indicated a strong pharmacodynamic correlation between plasma drug concentrations at 1 h after dosing and the reduction in the severity of depression as measured by the psychiatric rating scales. A minimum effective plasma concentration (MEC) of INN 00835 was 5 ng/ml. Statistically significant differences in response to treatment (P<0.05) were found between patients with plasma concentrations above MEC and those in the placebo group, as well as between subjects with plasma concentrations above and below the MEC. The peak effect was observed after the 5-day treatment and the response to treatment persisted during the 4-week follow-up period. The change of 5HT uptake rates after treatment was significantly larger in the drug-treated group than in the placebo group.. This was a pilot study conducted in a relatively small population (52 patients) and the limited number of blood sampling times did not allow a comprehensive pharmacokinetic analysis. There was a relatively large placebo response. The results have to be confirmed in future, large scale studies.. INN 00835 appears to be a promising drug for the treatment of major depression.

Topics: Adult; Antidepressive Agents; Biomarkers; Depressive Disorder, Major; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Middle Aged; Oligopeptides; Psychiatric Status Rating Scales; Retrospective Studies; Serotonin; Severity of Illness Index; Treatment Outcome