Results of two Phase 1, Randomized, Double-blind, Placebo-controlled, Studies (Ascending Single-dose and Multiple-dose Studies) to Determine the Safety, Tolerability, and Pharmacokinetics of Orally Administered LX9211 in Healthy Participants.

Purpose: For neuropathic pain, current therapies do not provide relief for most patients; less than half achieve a 50% pain reduction. Current analgesics have adverse effects. We present 2 Phase I studies of LX9211, a new small-molecule AP2-associated kinase 1 inhibitor with preclinical effectiveness in pain relief.

Long-Term Treatment with Telotristat Ethyl in Patients with Carcinoid Syndrome Symptoms: Results from the TELEPATH Study.

Introduction: Telotristat ethyl is indicated for use in combination with somatostatin analogs (SSAs) to treat carcinoid syndrome (CS) diarrhea uncontrolled by SSAs alone in adults, but long-term safety and efficacy data beyond 48 weeks are needed.

Objectives: The aims of the study were to evaluate the long-term safety and tolerability of telotristat ethyl and its effect on quality of life (QOL) in patients with CS.

Methods: In this phase 3, nonrandomized, multicenter, open-label, long-term extension study (TELEPATH), patients who participated in phase 2 or 3 trials of telotristat ethyl continued treatment at their present dose level (250 or 500 mg thrice daily) for 84 weeks.

Long-Term Safety Experience with Telotristat Ethyl Across Five Clinical Studies in Patients with Carcinoid Syndrome.

Background: Patients with neuroendocrine tumors (NETs) and carcinoid syndrome experience considerable morbidity and mortality; carcinoid syndrome may be associated with shorter survival. Carcinoid syndrome is linked to tumoral secretion of serotonin and other bioactive substances. The subsequent debilitating diarrhea and urgency to defecate pose significant health risks.

Telotristat ethyl in carcinoid syndrome: safety and efficacy in the TELECAST phase 3 trial.

Telotristat ethyl, a tryptophan hydroxylase inhibitor, was efficacious and well tolerated in the phase 3 TELESTAR study in patients with carcinoid syndrome (CS) experiencing ≥4 bowel movements per day (BMs/day) while on somatostatin analogs (SSAs). TELECAST, a phase 3 companion study, assessed the safety and efficacy of telotristat ethyl in patients with CS (diarrhea, flushing, abdominal pain, nausea or elevated urinary 5-hydroxyindoleacetic acid (u5-HIAA)) with <4 BMs/day on SSAs (or ≥1 symptom or ≥4 BMs/day if not on SSAs) during a 12-week double-blind treatment period followed by a 36-week open-label extension (OLE). The primary safety and efficacy endpoints were incidence of treatment-emergent adverse events (TEAEs) and percent change from baseline in 24-h u5-HIAA at week 12.

Insulin pen needles: effects of extra-thin wall needle technology on preference, confidence, and other patient ratings.

Background: Pen needles (PNs) are essential for insulin injections using pen devices. PN characteristics affect patients' injection experience.

Objective: The goal of this study was to evaluate the impact of a new extra-thin wall (XTW) PN versus usual PNs on overall patient preference, ease of injection, perceived time to complete the full dose, thumb button force to deliver the injection, and dose delivery confidence in individuals with diabetes mellitus (DM).

Simulated evaluation of a non-Luer safety connector system for use in neuraxial procedures.

Background: Spinal syringes, needles, and other devices with connectors that will not also connect with Luer devices could substantially reduce wrong-route drug administration errors. This study aimed to evaluate a newly designed non-Luer safety connector system for neuraxial procedures in terms of clinical acceptability and cross-connectivity with conventional Luer devices.

Methods: A non-Luer safety connector system (BD UniVia-6 Safety Connector system), which included non-Luer spinal needles, syringes, and blunt fill filter needles, was evaluated in a prospective, simulated use, randomized study.

Evaluation of a new safety peripheral IV catheter designed to reduce mucocutaneous blood exposure.

Objectives: We evaluated performance and clinical acceptability of a new peripheral intravenous catheter (PIVC) designed to reduce blood exposure.

Methods: A two phased, unblinded, randomized controlled trial was conducted at a clinical research center in New Jersey, USA. In Phase 1, clinicians were asked to evaluate two devices: a PIVC with blood control (BD Insyte Autoguard * BC [Blood Control] Shielded IV Catheter), and a reference conventional PIVC (BD Insyte Autoguard Shielded IV Catheter).

Comparative glycemic control, safety and patient ratings for a new 4 mm x 32G insulin pen needle in adults with diabetes.

Objective: Pen needles (PN) for subcutaneous insulin therapy have become smaller; 5 mm PNs are now the shortest in use. We evaluated the safety, efficacy and patient ratings of a new 4 mm x 32 gauge (G) PN.

Research Design And Methods: Subjects with type 1 and type 2 diabetes and HbA1c 5.

The antihypertensive efficacy of the combination of irbesartan and hydrochlorothiazide assessed by 24-hour ambulatory blood pressure monitoring. Irbesartan Multicenter Study Group.

In a multicenter, double-blind, randomized trial, 178 patients with ambulatory diastolic blood pressure (BP) > or =85 mm Hg and seated diastolic BP (SeDBP) 95-110 mm Hg received either once-daily irbesartan 75 mg/hydrochlorothiazide (HCTZ) 12.5 mg, irbesartan 150 mg/HCTZ 12.5 mg, or placebo for 8 weeks to assess reductions in 24-hour ambulatory BP and office BP.

Long-term safety and antihypertensive efficacy of irbesartan: pooled results of five open-label studies.

An analysis of 5 multicenter, open-label studies was conducted to evaluate the long-term safety and efficacy of irbesartan in 1,006 patients with seated diastolic blood pressure (SeDBP) 95-110 mm Hg. Irbesartan monotherapy was started at 75 mg and titrated to 300 mg at 2- to 4-week intervals to achieve normalized blood pressure (SeDBP <90 mm Hg). If normalized BP was not attained with irbesartan 300 mg alone, adjunctive medications could be added.

Matrix study of irbesartan with hydrochlorothiazide in mild-to-moderate hypertension.

The purpose of this study was to assess the safety and antihypertensive dose-response effects of irbesartan and hydrochlorothiazide (HCTZ) in patients with mild-to-moderate hypertension. After a 4- to 5-week single-blind placebo lead-in period, 683 patients with seated diastolic blood pressure (SeDBP) between 95 and 110 mm Hg were randomized to receive once-daily dosing with one of 16 different double-blind, fixed combinations of irbesartan (0, 37.5, 100, and 300 mg irbesartan) and HCTZ (0, 6.

Safety of irbesartan in the treatment of mild to moderate systemic hypertension.

Nine multicenter, randomized, placebo-controlled studies were conducted to evaluate the safety and tolerability of the angiotensin II subtype 1 receptor blocker (AT1 blocker) irbesartan for the treatment of mild to moderate hypertension. After a 4- to 5-week placebo lead-in phase, patients were randomized to 4 to 12 weeks of double-blind therapy with either placebo (n = 641) or irbesartan (n = 1,965) at doses of 1 to 900 mg orally. All doses of irbesartan were well tolerated with no evidence of dose-related adverse effects.

Dose-related efficacy of irbesartan for hypertension: an integrated analysis.

Results of eight multicenter, randomized, placebo-controlled, double-blind, parallel-group studies were pooled to assess the efficacy of the angiotensin II-receptor blocker irbesartan over the dose range of 1 to 900 mg. A total of 2955 adults with a seated diastolic blood pressure of 95 to 110 mm Hg were randomized to treatment with oral irbesartan once daily or placebo for 6 to 8 weeks. Office blood pressure was measured at trough (24+/-3 hours after the last dose) and peak (3+/-1 hours after the last dose) by mercury sphygmomanometry.

Dose-related antihypertensive effects of irbesartan in patients with mild-to-moderate hypertension.

Two multicenter, double-blind, placebo-controlled, parallel group studies were conducted to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of the angiotensin II receptor (AT1 subtype) antagonist irbesartan. The effect of irbesartan withdrawal and the effect of adding hydrochlorothiazide (HCTZ) to irbesartan were also assessed. After a placebo lead-in phase, all patients were randomized to 8 weeks of double-blind therapy with either placebo (n = 158) or irbesartan at doses of 1, 5, 10, 25, 50, 100, 200, or 300 mg (n = 731 total) orally once daily.

Comparative efficacy of two angiotensin II receptor antagonists, irbesartan and losartan in mild-to-moderate hypertension. Irbesartan/Losartan Study Investigators.

The primary objectives of this double-blind study were to compare the antihypertensive efficacy and tolerability of irbesartan and losartan, two angiotensin II (AT1 subtype) receptor antagonists with different pharmacokinetic profiles in patients with mild-to-moderate hypertension. Both drugs are approved for once-daily use (although losartan may also be prescribed twice-daily). After a placebo lead-in, 567 patients were randomized (1:1:1:1) to once-daily therapy with placebo, 100 mg losartan, 150 mg irbesartan, or 300 mg irbesartan for 8 weeks.

A randomised, double-blind comparison of the angiotensin II receptor antagonist, irbesartan, with the full dose range of enalapril for the treatment of mild-to-moderate hypertension.

Objective: To compare the anti-hypertensive efficacy, safety, and tolerability of irbesartan with those of the full dose range of enalapril in patients with mild-to-moderate hypertension.

Design And Methods: A total of 200 patients were randomised to irbesartan 75 mg or enalapril 10 mg (once daily). Doses were doubled at Weeks 4 and/or 8 if seated diastolic blood pressure (DBP) was > or = 90 mm Hg.

Comparison of the angiotensin II receptor antagonist irbesartan with atenolol for treatment of hypertension.

In this multicenter, double-blind study, the antihypertensive efficacy and safety of irbesartan were compared with those of atenolol in patients with mild-to-moderate hypertension. Following a 4- to 5-week placebo lead-in period, 231 patients with seated diastolic blood pressure (SeDBP) 95-110 mmHg were randomized to irbesartan 75 mg or atenolol 50 mg once daily for 24 weeks. Doses were doubled at Week 6 for SeDBP > or = 90 mmHg.

A multinational study of the effects of low-dose pravastatin in patients with non-insulin-dependent diabetes mellitus and hypercholesterolemia. Pravastatin Multinational Study Group for Diabetes.

This multinational, 16-week, randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of low-dose pravastatin in 325 patients with non-insulin-dependent diabetes mellitus (NIDDM) and hypercholesterolemia [serum total cholesterol concentrations of 5.2-7.8 mmol/l (200 to 300 mg/dl)].

Pravastatin experience in elderly and non-elderly patients.

Epidemiologic evidence linking elevated cholesterol concentrations and coronary heart disease (CHD) through the eighth decade of life provides a rationale for lowering cholesterol concentrations to reduce morbidity and mortality from CHD. Pravastatin, a well tolerated HMG CoA reductase inhibitor with a convenient once-daily dosing regimen, has been shown to effectively lower total and low density lipoprotein (LDL) cholesterol. Individual data from more than 1800 hypercholesterolemic patients enrolled in six double-blind, randomized, multicenter studies were pooled and then analyzed to compare the safety and efficacy of pravastatin in the elderly (i.