Safety, PK, and PD of recombinant anti-interleukin-21 monoclonal antibody in a first-in-human trial.

Objective: This first-in-human, randomized, double-blind, placebo-controlled trial assessed the safety of NNC0114-0005, a human recombinant anti interleukin (IL)-21 monoclonal antibody, for the treatment of rheumatoid arthritis (RA).

Methods And Materials: Healthy male subjects (HS (n = 44)) and patients with active RA treated with methotrexate (n = 20) were randomized 3 : 1 to single IV or SC doses of NNC0114-0005 (0.0025 - 25 mg/kg) or placebo.

Clinical and biological efficacy of recombinant human interleukin-21 in patients with stage IV malignant melanoma without prior treatment: a phase IIa trial.

Purpose: Human interleukin-21 (IL-21) is a class I cytokine that mediates activation of CD8(+) T cells, natural killer (NK) cells, and other cell types. We report final clinical and biological results of a phase II study of recombinant human IL-21 (rIL-21) in patients with metastatic melanoma.

Experimental Design: Open-label, single-arm, two-stage trial.

IL-21 induces in vivo immune activation of NK cells and CD8(+) T cells in patients with metastatic melanoma and renal cell carcinoma.

Purpose: Human interleukin-21 (IL-21) is a class I cytokine previously reported in clinical studies on immune responsive cancers. Here we report the effects of systemic IL-21 therapy on the immune system in two phase 1 trials with this novel cytokine.

Experimental Design: Recombinant IL-21 was administered by intravenous bolus injection at dose levels from 1 to 100 microg/kg using two planned treatment regimens: thrice weekly for 6 weeks (3/week); or once daily for five consecutive days followed by nine dose-free days (5 + 9).

An open-label, two-arm, phase I trial of recombinant human interleukin-21 in patients with metastatic melanoma.

Purpose: Human interleukin-21 (IL-21) is a pleiotropic class I cytokine that activates CD8(+) T cells and natural killer cells. We report a phase 1 study of recombinant human IL-21 in patients with surgically incurable metastatic melanoma. The primary objective was to investigate safety and tolerability by determining dose-limiting toxicity (DLT).

Ragaglitazar: the pharmacokinetics, pharmacodynamics, and tolerability of a novel dual PPAR alpha and gamma agonist in healthy subjects and patients with type 2 diabetes.

Ragaglitazar is a novel dual peroxisome proliferator-activated receptor (PPAR) alpha and gamma agonist intended to restore insulin sensitivity and correct diabetic dyslipidemia. These studies assessed single-dose pharmacokinetics and tolerability of ragaglitazar in healthy subjects, as well as multiple-dose pharmacokinetics, pharmacodynamics, and tolerability of ragaglitazar in healthy subjects and in patients with type 2 diabetes. Healthy subjects received a single oral dose (1-120 mg), and healthy subjects and type 2 diabetic patients received a loading dose and thereafter once-daily doses (0.

Safety and pharmacokinetics of ReN1869: a first human dose study in healthy subjects after single-dose administration.

ReN1869 (NNC 05-1869) is a novel, selective H1 receptor antagonist that has been developed for analgesic purposes. In a first human dose administration study, the safety and pharmacokinetics of seven single oral doses in the range of 3.5 to 95 mg ReN1869 were studied.

Levormeloxifene: safety, pharmacodynamics and pharmacokinetics in healthy postmenopausal women following single and multiple doses of a new selective oestrogen receptor modulator.

Aims: The safety, pharmacodynamics and pharmacokinetics of levormeloxifene, a selective oestrogen receptor modulator (SERM), were investigated in postmenopausal women following single doses and multiple dosing once daily up to 56 days.

Methods: The two randomized, double-blind, placebo controlled studies of six single ascending doses and at four multiple dose levels, respectively, included a total of 104 healthy postmenopausal women. Safety assessments comprised vital signs, ECG, haematology, clinical chemistry and reporting of adverse events.

Pharmacokinetics of levormeloxifene in young versus elderly postmenopausal women.

Background: Physiologic changes of aging may affect processes of drug absorption and distribution, in some cases necessitating age-dependent dose adjustment.

Objective: The possibility of age dependence in the pharmacokinetic behavior and tolerability of levormeloxifene was investigated in a single-center, open-label study.

Methods: The study comprised 2 groups of healthy postmenopausal women: group A included younger subjects (50-60 years) and group B included elderly subjects (> or = 66 years).

Tolerability, safety and pharmacokinetics of single dose and multiple dosing of the selective D1 antagonist NNC 01-0687 in healthy subjects.

Selective dopamine D1-receptor antagonists have been shown to exhibit similar effects in animal models for antipsychotic action as the selective D2 antagonists. NNC 01-0687, a benzazepine with selective and high affinity to the D1-receptor, was well tolerated by healthy subjects allocated to double blind, placebo controlled studies. Complaints of moderate restlessness and drowsiness were reported after administration of 25 mg NNC 01-0687, indicating the dose to be the maximum tolerated single dose.

PET examination of [11C]NNC 687 and [11C]NNC 756 as new radioligands for the D1-dopamine receptor.

The benzazepines NNC 687 and NNC 756 have in animal studies been described as selective D1-dopamine receptor antagonists. Both compounds have been labeled with 11C for examination by positron emission tomography (PET). In the present study central receptor binding was studied in monkeys and healthy men.

A tolerance study of single and multiple dosing of the selective dopamine uptake inhibitor GBR 12909 in healthy subjects.

GBR 12909 selectively blocks dopamine uptake and its biochemical and pharmacological profiles suggest that it may possess antidepressant activity and be of value in treatment of Parkinson's disease. The tolerance, pharmacokinetics and influence on psychomotor performance of GBR 12909 were investigated in a randomized placebo-controlled double-blind study. Four healthy subjects were administered oral single doses of 100, 200 and 300 mg GBR 12909 and placebo, and four other healthy subjects received, 50, 100 and 150 mg GBR 12909 and placebo once daily for 7 days.

Inhibition of photosensitive seizures in man by the beta-carboline, ZK 95962, a selective benzodiazepine receptor agonist.

A single-dose study of the beta-carboline, ZK 95962, on photosensitive generalized paroxysmal activity in the EEG was conducted in 6 patients with primary generalized epilepsy. Four of the patients were newly diagnosed and did not receive any antiepileptic drug or other medication during the study. Two were receiving current therapy with carbamazepine.

Cardiovascular (ECG and systolic time intervals) and anticholinergic effects of repeated doses of femoxetine--a comparison with amitriptyline and placebo in healthy men.

1. The cardiovascular and anticholinergic effects of femoxetine and amitriptyline were compared with those of placebo in a double-blind cross-over trial in 12 healthy men. The daily doses administered were therapeutic: 600 mg femoxetine and 150 mg amitriptyline.

Femoxetine in the treatment of obese patients in general practice. A randomized group comparative study with placebo.

A study was carried out in general practice to compare the effectiveness of femoxetine, a selective serotonin reuptake inhibitor, with the effect of placebo in helper patients more than 20 per cent above their ideal weight to lose weight. Patients were allocated at random to receive either 600 mg femoxetine (36 patients) or placebo (37 patients) daily over a period of 16 weeks. They were also asked to restrict their calorie intake to 1200-1600 kcal.

Femoxetine and amitriptyline in general practice: a randomized double-blind group comparison.

Patients with a depressive illness with 4 major symptoms of depression and a score of at least 17 on the Hamilton Depression Scale (1-17) (HDS) were allocated to a randomized double-blind group comparative study in general practice. After retrospective analysis, all 81 patients except one were characterized as suffering from a 'Definite Major Depressive Disorder', as defined by Spitzer et al. (1978).