Safety and tolerability of single intravenous doses of T cell modulatory peptide (TCMP-80) in healthy volunteers.

Abstract:

:T Cell Modulatory Peptide (TCMP-80), L-lysine-L-serine, is a synthetic dipeptide structurally related to a selected amino acid sequence in human immunoglobulin G. Based on in vitro and preclinical in vivo testing, TCMP-80 has immunomodulatory properties. This report describes the first administration of TCMP-80 to man in a randomized, double-blind, placebo-controlled, single rising-dose tolerability trial. Healthy male volunteers received TCMP-80 or placebo as a 10-minute intravenous infusion. At weekly intervals, two of four subjects were given TCMP-80; the remaining two received placebo. Each subject could receive only one dose during the study. Dosing started at 0.01 mg/kg and was increased to 0.03, 0.1, 0.3, 1, 3, 6.5, and 10 mg/kg. CBCs, blood chemistries, urinalyses, and lymphocyte subset populations were monitored predose and postdose on Days 1, 5, and 14. Three placebo and three TCMP-80 subjects reported adverse events. Adverse events reported after TCMP-80 administration were mild in nature (headache, dizziness, hematoma at injection site), appeared to be independent of dose, and resolved without medical intervention. No clinically significant alterations in vital signs, physical examination parameters, or clinical laboratory values were observed. Based on the results of this study, TCMP-80 is safe and well-tolerated within the dose range studied when administered as single intravenous infusions. Additionally, this study design represents an approach to assess the safety of an investigational immunomodulatory drug.

journal_name

J Clin Pharmacol

authors

Eldon MA,Smith RA,Leese PT,Daigle AE,Katz DV,Richieri SP

doi

10.1002/j.1552-4604.1990.tb03605.x

subject

Has Abstract

pub_date

1990-04-01 00:00:00

pages

352-7

issue

4

eissn

0091-2700

issn

1552-4604

journal_volume

30

pub_type

临床试验,杂志文章,随机对照试验
  • A Cross-Study Analysis Evaluating the Effects of Food on the Pharmacokinetics of Rivaroxaban in Clinical Studies.

    abstract::US prescribing guidelines recommend that 15- and 20-mg doses of rivaroxaban be administered with food for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) and for reduction in the risk of recurrence of DVT and PE. In addition, the US prescribing guidelines recommend these doses be administered w...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/jcph.958

    authors: Zhang L,Peters G,Haskell L,Patel P,Nandy P,Moore KT

    更新日期:2017-12-01 00:00:00

  • Tricenter assessment of the efficacy of the ACE inhibitor, moexipril, by ambulatory blood pressure monitoring.

    abstract::To assess the efficacy and time-dependent effects of once-daily moexipril, a nonsulfhydryl ester prodrug of the angiotensin-converting enzyme (ACE) inhibitor, moexiprilat, we conducted a multicenter, double-blind, placebo-controlled trial in 51 hypertensive patients using both clinic and ambulatory blood pressure (BP)...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验

    doi:10.1002/j.1552-4604.1995.tb04052.x

    authors: White WB,Whelton A,Fox AA,Stimpel M,Kaihlanen PM

    更新日期:1995-03-01 00:00:00

  • A Population Pharmacokinetic Model of Oral Docetaxel Coadministered With Ritonavir to Support Early Clinical Development.

    abstract::Oral administration of docetaxel is an attractive alternative for conventional intravenous (IV) administration. The low bioavailability of docetaxel, however, hinders the application of oral docetaxel in the clinic. The aim of the current study was to develop a population pharmacokinetic (PK) model for docetaxel and r...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/jcph.1532

    authors: Yu H,Janssen JM,Sawicki E,van Hasselt JGC,de Weger VA,Nuijen B,Schellens JHM,Beijnen JH,Huitema ADR

    更新日期:2020-03-01 00:00:00

  • Dosing Recommendations for Pediatric Patients With Renal Impairment.

    abstract::A treatment gap exists for pediatric patients with renal impairment. Alterations in renal clearance and metabolism of drugs render standard dosage regimens inappropriate and may lead to drug toxicity, but these studies are not routinely conducted during drug development. The objective of this study was to examine the ...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/jcph.1676

    authors: Al-Khouja A,Park K,Anderson DJC,Young C,Wang J,Huang SM,Khurana M,Burckart GJ

    更新日期:2020-12-01 00:00:00

  • Single- and multiple-dose pharmacokinetics of dezocine in patients with acute or chronic pain.

    abstract::The pharmacokinetic properties of dezocine were examined in 15 patients with acute or chronic pain. In 3 groups of 5 patients each, serum levels were determined at various intervals after single intravenous doses of 5, 10, and 20 mg. After these single doses, dezocine was very rapidly distributed (mean t1/2 alpha less...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1002/j.1552-4604.1995.tb04080.x

    authors: Wilson JM,Cohen RI,Kezer EA,Schange SJ,Smith ER

    更新日期:1995-04-01 00:00:00

  • The role of the clinical pharmacist in medical education.

    abstract::The clinical pharmacist is an integral member of the Docent team at the University of Missouri--Kansas City School of Medicine with duties in both teaching and patient care. These doctoral-level clinical pharmacists have sole responsibility for providing instruction in basic pharmacology and pharmacokinetics and for t...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1981.tb05700.x

    authors: Covinsky JO

    更新日期:1981-04-01 00:00:00

  • Improving the diagnosis of hypersensitivity reactions associated with sulfonamides.

    abstract::The differential diagnosis of idiosyncratic adverse drug reactions (ADRs) is difficult because symptoms are seldom pathognomonic. The authors compared the performance of two new diagnostic aids in the differential diagnosis of 27 cases of skin reactions associated with sulfonamide therapy. One test, the Bayesian Adver...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1994.tb04736.x

    authors: Lanctôt KL,Ghajar BM,Shear NH,Naranjo CA

    更新日期:1994-12-01 00:00:00

  • Metabolic studies in patients with nadolol: oral and intravenous administration.

    abstract::Nadolol-14C, 2,3-cis-5-(3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy)-1,2,3,4-tetrahydro-2,3-naphthalenediol, a nonselective beta-adrenergic blocking agent, was administered orally and intravenously at 2-mg doses to patients with mild cases of essential hypertension. Terminal plasma half-times after oral and intraven...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1977.tb04609.x

    authors: Dreyfuss J,Brannick LJ,Vukovich RA,Shaw JM,Willard DA

    更新日期:1977-05-01 00:00:00

  • Application of preclinical data to initiate the modified continual reassessment method for maximum tolerated dose-finding trials.

    abstract::This study was conducted to evaluate whether the allometric approach can be used to predict maximum tolerated dose (MTD) in humans from animal data. Twenty-five anticancer drugs were taken from the literature and used in this analysis. The results of the study indicate that MTD can be predicted with reasonable accurac...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1177/00912700122009791

    authors: Mahmood I

    更新日期:2001-01-01 00:00:00

  • Pharmacology and pharmacokinetics of amiodarone.

    abstract::Amiodarone is a unique antiarrhythmic agent originally developed as a vasodilator. Classified electrophysiologically as a Type III antiarrhythmic, it also has both nonspecific antisympathetic and direct, fast channel-membrane effects. Hemodynamic effects of orally administered amiodarone (a negative inotropic agent) a...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1002/j.1552-4604.1991.tb03673.x

    authors: Freedman MD,Somberg JC

    更新日期:1991-11-01 00:00:00

  • Pharmacokinetics of tinidazole in male and female subjects.

    abstract::Tinidazole is a potent nitroimidazole compound active against, and used to treat, Trichomonas vaginalis infections in males and females. Speculation exists in the literature that observed differences in tinidazole plasma concentrations between males and females may be due to sex-mediated pharmacokinetic differences. T...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1982.tb02650.x

    authors: Chaikin P,Alton KB,Sampson C,Weintraub HS

    更新日期:1982-11-01 00:00:00

  • Pharmacology of acetylcholinesterase inhibitors and N-methyl-D-aspartate receptors for combination therapy in the treatment of Alzheimer's disease.

    abstract::The search for effective treatments of Alzheimer's disease (AD) is one of the major challenges facing modern medicine. Acetylcholinesterase (AChE) inhibitors (AChEIs) are effective for the treatment of mild to moderate AD, and memantine, an N-methyl-D-aspartate (NMDA) inhibitor, has been approved for moderate to sever...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1177/0091270006288734

    authors: Geerts H,Grossberg GT

    更新日期:2006-07-01 00:00:00

  • Influence of body weight and gender on the pharmacokinetics, pharmacodynamics, and antihypertensive efficacy of aliskiren.

    abstract::Gender and body weight influence the pharmacokinetics and pharmacodynamics of many drugs. This pooled analysis of 17 clinical studies evaluated the effect of gender, body mass index (BMI), body weight, and lean body weight (LBW) on the pharmacokinetics of the direct renin inhibitor aliskiren in healthy volunteers (n =...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1177/0091270009359525

    authors: Jarugula V,Yeh CM,Howard D,Bush C,Keefe DL,Dole WP

    更新日期:2010-12-01 00:00:00

  • Pharmacokinetics of cefprozil in healthy subjects and patients with renal impairment.

    abstract::Cefprozil, a new broad-spectrum oral cephalosporin, is composed of cis and trans isomers in an approximate 90:10 ratio. The pharmacokinetics of a single oral 1000-mg dose of cefprozil were evaluated in 6 healthy subjects and 24 patients with various degrees of renal impairment. Six of these subjects were studied both ...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1002/j.1552-4604.1991.tb03719.x

    authors: Shyu WC,Pittman KA,Wilber RB,Matzke GR,Barbhaiya RH

    更新日期:1991-04-01 00:00:00

  • Small animal model of weightlessness for pharmacokinetic evaluation.

    abstract::As the United States seeks a greater presence in space, physiologic changes associated with space flight become of greater concern. Exposure to a weightless environment has been shown to have numerous effects on body composition and organ function. Alterations include decreases in muscle and liver mass, changes in bon...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1002/j.1552-4604.1994.tb02023.x

    authors: Feldman S,Brunner LJ

    更新日期:1994-06-01 00:00:00

  • Trial treatment length optimization with an emphasis on disease progression studies.

    abstract::Optimal design has been used in the past mainly to optimize sampling schedules for clinical trials. Optimization on design variables other than sampling times has been published in the literature only once before. This study shows, as an example, optimization on the length of treatment periods to obtain reliable estim...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1177/0091270008329560

    authors: Hennig S,Nyberg J,Hooker AC,Karlsson MO

    更新日期:2009-03-01 00:00:00

  • Short-term effects of cannabinoids on immune phenotype and function in HIV-1-infected patients.

    abstract::Cannabinoids, including smoked marijuana and delta9-tetrahydrocannabinol (THC) (dronabinol, Marinol), have been used to treat human immunodeficiency virus-1 (HIV)-associated anorexia and weight loss. Concerns have been raised, however, that these compounds might have adverse effects on the immune system of subjects wi...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1002/j.1552-4604.2002.tb06007.x

    authors: Bredt BM,Higuera-Alhino D,Shade SB,Hebert SJ,McCune JM,Abrams DI

    更新日期:2002-11-01 00:00:00

  • Effects of hetastarch and albumin on coagulation in patients with septic shock.

    abstract::The effect of 6% hydroxyethyl starch (hetastarch) and 5% human serum albumin (albumin) infusion on coagulation in 12 patients with septic shock was evaluated. Patients were randomly assigned to receive either albumin (N = 6) or hetastarch (N = 6) infusion over a 24-hour study interval. The prothrombin time (PT), parti...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1002/j.1552-4604.1988.tb05751.x

    authors: Falk JL,Rackow EC,Astiz ME,Weil MH

    更新日期:1988-05-01 00:00:00

  • Effect of a new beta-adrenergic blocker, l-bunolol, on blood pressure and on the renin-aldosterone system.

    abstract::The antihypertensive effect of a new beta-adrenergic receptor blocker, l-bunolol, was evaluated in 11 hospitalized hypertensive patients of whom four belonged to the high-renin, five to the normal-renin, and two to the low-renin subgroup. There was a significant decrease in blood pressure in most patients, often to no...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1002/j.1552-4604.1977.tb04615.x

    authors: Gavras H,Gavras I,Brunner HR,Laragh JH

    更新日期:1977-05-01 00:00:00

  • Evaluation of sex differences in the pharmacokinetics of ranitidine in humans.

    abstract::A bioequivalence study of two oral formulations of 300 mg ranitidine was carried out in 16 healthy volunteers (8 men and 8 women), and the pharmacokinetics in both sexes were compared. There was bioequivalence of both formulations. The terminal half-life of ranitidine was 7% shorter and the oral apparent clearance 10....

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1002/j.1552-4604.1996.tb04245.x

    authors: Abad-Santos F,Carcas AJ,Guerra P,Govantes C,Montuenga C,Gómez E,Fernández A,Frias J

    更新日期:1996-08-01 00:00:00

  • Mycophenolate mofetil in islet cell transplant: variable pharmacokinetics but good correlation between total and unbound concentrations.

    abstract::The authors investigated the pharmacokinetics of mycophenolic acid over 1 year in 8 Caucasian women undergoing islet cell transplantation. Total mycophenolic acid AUC(0-12) mcg x h/mL before day 60 was 62.1-67.8, declining to 33.6-64.7 thereafter (P = .61). Median total trough concentrations were 1.16-2.90 mcg/mL. Unb...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1177/0091270005278599

    authors: Jacobson PA,Green KG,Hering BJ

    更新日期:2005-08-01 00:00:00

  • In vitro P-glycoprotein interactions and steady-state pharmacokinetic interactions between tolvaptan and digoxin in healthy subjects.

    abstract::Interactions between tolvaptan and digoxin were determined in an open-label, sequential study where 14 healthy subjects received tolvaptan 60 mg once daily (QD) on days 1 and 12 to 16 and digoxin 0.25 mg QD on days 5 to 16. Mean maximal concentrations (C(max)) and area under the curve during the dosing interval (AUC(τ...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1177/0091270010376193

    authors: Shoaf SE,Ohzone Y,Ninomiya S,Furukawa M,Bricmont P,Kashiyama E,Mallikaarjun S

    更新日期:2011-05-01 00:00:00

  • The effect of renal insufficiency and hemodialysis on the pharmacokinetics of nalmefene.

    abstract::The disposition of nalmefene, an opioid antagonist intended for the reversal of opioid-induced respiratory depression, and its primary metabolite nalmefene glucuronide, were characterized in adult volunteers with normal renal function and in patients with end-stage renal disease (ESRD). The effect of hemodialysis on t...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1996.tb04179.x

    authors: Matzke GR,Frye RF,Alexander AC,Reynolds R,Dixon R,Johnston J,Rault RM

    更新日期:1996-02-01 00:00:00

  • Aprepitant pharmacokinetics and assessing the impact of aprepitant on cyclophosphamide metabolism in cancer patients undergoing hematopoietic stem cell transplantation.

    abstract::Aprepitant, a neurokinin antagonist, is an effective antiemetic agent in chemotherapy for delayed nausea and vomiting. The study objective was to evaluate the pharmacokinetics of aprepitant and concurrent cyclophosphamide (CY), often a component of hematopoietic stem cell transplant (HSCT) conditioning regimen, in can...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1177/0091270011398243

    authors: Bubalo JS,Cherala G,McCune JS,Munar MY,Tse S,Maziarz R

    更新日期:2012-04-01 00:00:00

  • Cardiovascular effects of H2-receptor antagonists.

    abstract::The type II histamine receptor antagonists, cimetidine and ranitidine, widely used in treatment of peptic ulcer disease have been reported to cause bradycardia. To evaluate the cardiovascular effects of H2 antagonists nineteen healthy volunteers were entered into a double-blind crossover comparison of cimetidine 300 m...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1002/j.1552-4604.1989.tb03365.x

    authors: Hughes DG,Dowling EA,DeMeersman RE,Garnett WR,Karnes HT

    更新日期:1989-05-01 00:00:00

  • Pharmacokinetics, safety, and tolerability of the oral Renin inhibitor aliskiren in patients with hepatic impairment.

    abstract::Aliskiren is the first in a new class of orally active, direct renin inhibitors for the treatment of hypertension. This open-label, nonrandomized, single-center, parallel-group study compared the pharmacokinetics and safety of a single 300-mg oral dose of aliskiren in patients with mild, moderate, or severe hepatic im...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1177/0091270006294404

    authors: Vaidyanathan S,Warren V,Yeh C,Bizot MN,Dieterich HA,Dole WP

    更新日期:2007-02-01 00:00:00

  • Computer-assisted molecular modeling: indispensable tools for molecular pharmacology.

    abstract::Ball-and-stick mechanical models, typically associated with chemists, have been helpful in understanding structural problems and the relationship between structure and biologic activity. With progress in computer speed, graphics performance, and software innovation, molecules of biological interest can be subjected to...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1002/j.1552-4604.1993.tb03915.x

    authors: Bowen JP,Charifson PS,Fox PC,Kontoyianni M,Miller AB,Schnur D,Stewart EL,Van Dyke C

    更新日期:1993-12-01 00:00:00

  • Efficacy of acebutolol in chronic stable angina using single-blind and randomized double-blind protocol.

    abstract::The clinical effects of a cardioselective beta-adrenergic blocking drug, acebutolol, were studied in 25 patients with chronic stable angina, using a seven-week single-blind placebo leads to acebutolol (mean dose 913 mg/day) phase followed by 12-week randomized double-blind placebo leads to acebutolol (mean dose 968 mg...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1002/j.1552-4604.1982.tb02688.x

    authors: Lee G,DeMaria AN,Favrot L,Hermanovich J,Kozina J,Krieg P,Kimchi A,Laddu A,Mason DT

    更新日期:1982-08-01 00:00:00

  • The effect of triple drug therapy on renal function in patients with essential hypertension.

    abstract::The effects of long-term triple drug therapy on renal function in patients with moderate to severe essential hypertension have not been evaluated systematically. We prospectively studied fifteen male patients with moderate to severe essential hypertension receiving triple drug therapy (metolazone, atenolol or betaxolo...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1989.tb03423.x

    authors: Reams GP,Bauer JH

    更新日期:1989-09-01 00:00:00

  • Effect of Renal Function Impairment on the Pharmacokinetics, Safety, and Tolerability of the Iminosugar Sinbaglustat.

    abstract::Sinbaglustat (ACT-519276), a brain-penetrating inhibitor of glucosylceramide synthase and nonlysosomal glucosylceramidase, is developed as a new therapy for lysosomal storage disorders. In the first-in-human study, sinbaglustat was primarily excreted unchanged in urine. This study was conducted to evaluate the effect ...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/jcph.1808

    authors: Melchior M,Dingemanse J,Alatrach A,Feldkamp T,Sidharta PN,Géhin M

    更新日期:2020-12-23 00:00:00