A double-blind, placebo-controlled, efficacy, safety, and pharmacokinetic study of INN 00835, a novel antidepressant peptide, in the treatment of major depression

Feighner, John P.; Ehrensing, Rudolph H.; Kastin, Abba J.; Leonard, Brian E.; Sverdlov, Lev; Nicolau, G.; Patel, Asha; Hlavka, J.; Abajian, H.; Noble, John F.

doi:10.1016/s0165-0327(99)00187-1

Cited by 17 publications

(8 citation statements)

References 12 publications

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“…It was also shown that the FRL rats were unaffected by chronic treatment with 0.3 mg/ kg nemifitide, a dose that reduced immobility in the FSL rats. Thus, nemifitide produces a pattern similar to other antidepressants, with changes occurring in only the FSL rat (Feighner et al, 2000a). Nemifitide is a novel antidepressant that has shown promise in human subjects.…”

Section: Nemifitide Mif Analogmentioning

confidence: 88%

The Flinders Sensitive Line rat: A selectively bred putative animal model of depression

Overstreet

Friedman

Mathé

et al. 2005

Neuroscience & Biobehavioral Reviews

337

267

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Section: Nemifitide Mif Analogmentioning

confidence: 88%

The Flinders Sensitive Line rat: A selectively bred putative animal model of depression

Overstreet

Friedman

Mathé

et al. 2005

Neuroscience & Biobehavioral Reviews

337

267

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“…The determination of peptide stability in galenic formulations is necessary for development of optimum delivery systems [20,21,22]. Analysis of pharmacokinetic data for compound resorption, distribution, protein binding, and elimination in vivo requires time-dependent determination of peptide concentrations in plasma [2,23,24,25,26]. Furthermore, pharmacodynamic data and bioavailability of the drugs have to be investigated.…”

Section: Introductionmentioning

confidence: 99%

Analytical procedures for quantification of peptides in pharmaceutical research by liquid chromatography?mass spectrometry

John¹,

Walden²,

Schäfer³

et al. 2004

Analytical and Bioanalytical Chemistry

155

104

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Peptide quantification by liquid chromatography-mass spectrometry (LC-MS) combines the high resolving power of reversed-phase (RP) chromatography with the excellent selectivity and sensitivity of mass spectrometric detection. On the basis of comprehensive practical experience in the analysis of small molecules, pharmaceutical research is developing technologies for analysis of a growing number of peptidic drug candidates. This article is a detailed review of procedures based on LC-MS techniques for quantitative determination of peptides. With the focus on pharmaceutical applications several technologies for sample preparation, various aspects of peptide chromatography, important characteristics of ESI-MS, selectivity of MS-detection modes, the large variability of internal standards, and modern instrumentation are discussed. The demand for reliable, robust, sensitive, and accurate methods is discussed using numerous examples from the literature, complemented by experiments and results from our laboratory.

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“…The lack of adverse events in these studies (data on file) allowed the administration of similar doses in the first two efficacy studies reported separately [2][3][4][5].…”

Section: Methodsmentioning

confidence: 99%

“…Nemifitide is the lead compound in a series of highly potent small-chain peptides synthesized at Innapharma [1]. In two previously conducted pilot phase 2 double-blind, placebo-controlled trials [2][3][4][5] nemifitide was administered subcutaneously for 5 or 10 days to patients diagnosed with major depression. The doses administered in these studies were similar: 18 mg/patient and 0.2 mg/kg, respectively.…”

Section: Introductionmentioning

confidence: 99%

Clinical pharmacokinetic studies with INN 00835 (Nemifitide), a novel pentapeptide antidepressant

Feighner

Nicolau

Abajian

et al. 2002

Biopharm & Drug Disp

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Nemifitide (4-fluoro-L-phenylalanyl-trans-4-hydroxy-L-prolyl-L-arginylglycyl-L-tryptophanamide ditrifluoroacetate) is a novel antidepressant, currently in phase 2/3 clinical trials. The purpose of our phase 1 clinical trials (conducted over a three year period) was to provide safety and pharmacokinetic data to support its clinical development as an antidepressant drug. Single and multiple doses ranging from 18 to 320 mg were administered subcutaneously to healthy volunteers in five phase 1 studies. Plasma concentrations of unchanged parent drug were determined by a validated LC/MS/MS method in blood samples collected at timepoints between 10 min and 72 h after dosing. Nemifitide was rapidly absorbed (C(max) at 10 min) and eliminated (t(1/2) 15-30 min) in most subjects. Regression and power model analyses were used to evaluate the data. The results indicate that pharmacokinetic parameters: AUC(0-t), AUC (0-infinity) and C(max), were close to dose proportional in the dose range investigated. There was no evidence of systemic accumulation of drug following 5 daily doses. No serious adverse events or clinically significant systemic adverse events occurred at any of the doses investigated in the over 100 subjects dosed in these studies. Drug-related adverse events were limited to local and transient skin reactions (pain and/or erythema) at the injection site, especially at the high doses administered: 240 and 320 mg.

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A double-blind, placebo-controlled, efficacy, safety, and pharmacokinetic study of INN 00835, a novel antidepressant peptide, in the treatment of major depression

Cited by 17 publications

References 12 publications

The Flinders Sensitive Line rat: A selectively bred putative animal model of depression

The Flinders Sensitive Line rat: A selectively bred putative animal model of depression

Analytical procedures for quantification of peptides in pharmaceutical research by liquid chromatography?mass spectrometry

Clinical pharmacokinetic studies with INN 00835 (Nemifitide), a novel pentapeptide antidepressant

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