Clinical Drug Investigation (CLIN DRUG INVEST )

Description

Clinical Drug Investigation gives you rapid access to the best designed, peer reviewed clinical and pharmacoeconomic studies worldwide, allowing you to keep up to date with the latest original research in this exciting area. The Journal's aim is rapid publication of original research covering all phases of clinical drug development and therapeutic use of drugs. This includes clinical trials, outcomes research, clinical pharmacoeconomic studies, pharmacoepidemiology studies with a strong link to optimum prescribing practice for a drug or group of drugs, clinical pharmacodynamic and clinical pharmacokinetic studies with a strong link to clinical practice and, in some instances, pharmacodynamic or pharmacokinetic studies in healthy volunteers, but in which some established or purported implications for clinical prescribing are discussed. In addition, short communications and case study reports that meet these criteria are also encouraged, as are letters to the editor.

  • Impact factor
    1.92
  • 5-year impact
    1.64
  • Cited half-life
    4.90
  • Immediacy index
    0.36
  • Eigenfactor
    0.00
  • Article influence
    0.43
  • Website
    Clinical Drug Investigation website
  • ISSN
    1179-1918
  • OCLC
    31920475
  • Material type
    Periodical, Internet resource
  • Document type
    Journal / Magazine / Newspaper, Internet Resource

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Pitavastatin is the latest statin to be approved and has shown beneficial effects on plasma lipid profiles. The aim of the present meta-analysis was to assess both the efficacy and safety of pitavastatin versus simvastatin, one of the most commonly used statins.
    Clinical Drug Investigation 07/2014;
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    ABSTRACT: Hypertension is one of the most common co-existing conditions in patients with chronic pain, and the potential effects of an analgesic on heart rate and blood pressure are of particular concern for patients with hypertension. The purpose of this analysis was to evaluate changes in blood pressure and heart rate with tapentadol extended release (ER) treatment in patients with hypertension.
    Clinical Drug Investigation 06/2014;
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    ABSTRACT: The effectiveness and tolerability of tapentadol extended release (ER), a centrally acting analgesic with μ-opioid receptor agonist and norepinephrine (noradrenaline) reuptake inhibitor activities, have been demonstrated in patients with chronic pain, including those switching directly from prior opioid therapy. The objective of the current study was to evaluate the effectiveness and safety of conversion to oral tapentadol ER (50-250 mg twice daily) from previous around-the-clock strong opioid therapy in patients with moderate to severe, chronic malignant tumor-related cancer pain that was well-controlled.
    Clinical Drug Investigation 06/2014;
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    ABSTRACT: Latanoprost is an ester prodrug prostaglandin F2α analogue that is a selective agonist of endogenous prostanoid FP receptors and that reduces intraocular pressure (IOP) by increasing the uveoscleral outflow of aqueous humour. Preservative-free (PF) latanoprost [Monoprost(®)] is a new formulation of latanoprost that is approved for use in the EU in patients with primary open-angle glaucoma (POAG)/ocular hypertension. This article reviews the clinical pharmacology of this new formulation, focussing on its efficacy and tolerability in this indication. PF latanoprost was efficacious in reducing IOP in a randomized, investigator-masked, multinational trial in patients with POAG/ocular hypertension (n = 404). At days 15, 42 and 84 of follow-up, PF latanoprost was noninferior to benzalkonium chloride-preserved (BAK) latanoprost in terms of reductions in IOP. In this trial, at days 42 and 84 the proportions of patients with conjunctival hyperaemia were significantly lower with PF latanoprost than with BAK latanoprost. Patient subjective ratings of ocular symptoms were also significantly lower with PF latanoprost than with BAK latanoprost. In the absence of head-to-head comparisons with other anti-glaucoma drugs, an adjusted, indirect comparison meta-analysis was performed using data from 21 randomized clinical trials in patients with POAG/ocular hypertension. Based on this analysis, PF latanoprost had similar efficacy to different formulations of three comparator prostaglandin analogues in reducing the patient's IOP and was associated with a significantly lower risk of developing hyperaemia/ocular redness than these comparators. PF latanoprost offers a useful alternative to the available preserved prostaglandin analogues for the treatment of POAG/ocular hypertension.
    Clinical Drug Investigation 06/2014;
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    ABSTRACT: Macitentan is a novel dual endothelin receptor antagonist recently approved for the treatment of pulmonary arterial hypertension (PAH). Warfarin, an anticoagulant often prescribed to patients with PAH, has a narrow therapeutic index and is prone to potential interactions with drugs. This study assessed the effects of macitentan on the pharmacokinetics and pharmacodynamics of single-dose warfarin in healthy subjects.
    Clinical Drug Investigation 05/2014;
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    ABSTRACT: The treatment of hyperlipidaemia in human immunodeficiency virus (HIV)-infected patients has become increasingly important. However, treatment options are limited because of the drug-drug interaction between certain statins and HIV medications metabolized by cytochrome P450 (CYP) enzymes. The primary objective was to investigate the steady-state pharmacokinetics of pitavastatin when co-administered with darunavir/ritonavir. The secondary objective was to investigate the steady-state pharmacokinetics of both darunavir and ritonavir when co-administered with pitavastatin. This was a single-centre, open-label, multi-dose, fixed-sequence study in HIV seronegative healthy volunteers. Pitavastatin 4 mg was administered once daily on days 1-5 and on days 12-16, and darunavir 800 mg/ritonavir 100 mg once daily on days 6-16. Pharmacokinetic blood sampling was performed on days 5, 11 and 16. No significant interaction was concluded if the 90 % confidence intervals (CIs) of the geometric mean ratios (GMRs) for total exposure [i.e. the area under the plasma concentration-time curve over a dosing interval at steady state (AUC0-τ )] and for peak exposure [i.e. the maximum plasma concentration (C max)] of the two treatments were within the 80-125 % range. Twenty-eight subjects (mean age 30.5 years) were enrolled, and pharmacokinetic data were available for 27 subjects. For pitavastatin, the GMRs and 90 % CIs for the AUC0-τ and C max ratios with co-administration were 0.74 (0.69-0.80) and 0.96 (0.84-1.09), respectively. For both darunavir and ritonavir, the 90 % CIs for the AUC0-τ and C max ratios were within 80-125 % with pitavastatin co-administration. No significant safety issues were reported. Darunavir/ritonavir decreased total exposure to pitavastatin by 26 %, while peak exposures were similar. Pitavastatin did not influence the pharmacokinetics of darunavir or ritonavir. There is limited interaction between pitavastatin and darunavir/ritonavir.
    Clinical Drug Investigation 05/2014;
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    ABSTRACT: In patients undergoing induction chemotherapy for acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS), posaconazole has been proven more effective in the prevention of invasive fungal infection (IFI) than fluconazole or itraconazole (standard azoles) The current analysis seeks to estimate the cost effectiveness of prophylactic posaconazole compared with standard azoles in AML or MDS patients with severe chemotherapy-induced neutropenia in Sweden. A decision-analytic model was used to estimate life expectancy, costs, and quality-adjusted life-years (QALYs). Efficacy data were derived from a phase III clinical trial. Life expectancy and quality of life data were collected from the literature. A modified Delphi method was used to gather expert opinion on resource use for an IFI. Unit costs were captured from hospital and pharmacy pricelists. A probabilistic sensitivity analysis (PSA) was used to investigate the impact of uncertainty in the model parameters on the cost-effectiveness results. The estimated mean direct cost per patient with posaconazole prophylaxis was 46,893 Swedish kronor (SEK) ( 5,387) and SEK50,017 ( 5,746) with standard azoles. Prophylaxis with posaconazole resulted in 0.075 QALYs gained compared with standard azoles. At a cost-effectiveness threshold of SEK500,000/QALY the PSA demonstrated a more than 95 % probability that posaconazole is cost effective versus standard azoles for the prevention of IFI in high-risk neutropenic patients in Sweden. Given the assumptions, methods, and data used, posaconazole is expected to be cost effective compared with standard azoles when used as antifungal prophylaxis in AML or MDS patients with chemotherapy-induced prolonged neutropenia in Sweden.
    Clinical Drug Investigation 05/2014;
  • Clinical Drug Investigation 05/2014;
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    ABSTRACT: Diabetes mellitus is a complex, progressive disease that can lead to complications if it is not strictly controlled. The literature suggests that only 50 % of Italian patients with type 2 diabetes mellitus (T2DM) achieve guideline-recommended levels of glycaemic control, suggesting that treatment regimens need to be improved. The present study aimed to evaluate the effectiveness of dipeptidyl peptidase-4 (DPP-4) inhibitors in terms of glycaemic control, body weight and lipid profile in a series of patients with T2DM attending a diabetes outpatient facility. This was an observational retrospective study performed on a series of patients with T2DM attending our three outpatient clinics. The study included 360 patients with T2DM of both sexes, aged between 30 and 85 years, with a body mass index (BMI) of 22-45 kg/m(2) who were uncontrolled [glycated haemoglobin (HbA1c) 7.1-10 %] despite dietary restrictions or treatment with pharmacological therapy. Patients included in the analysis received therapy with a DPP-4 inhibitor (sitagliptin, n = 244; vildagliptin, n = 97; saxagliptin, n = 19). Vildagliptin reduced HbA1c by 1.2 % compared with sitagliptin and saxagliptin (-0.9 %) from a baseline of 8 % (similar in all groups). The greatest decrease in fasting plasma glucose was seen with vildagliptin (-37 mg/dL) compared with sitagliptin and saxagliptin (-20 and -29 mg/dL, respectively). A greater reduction in total cholesterol was achieved with vildagliptin (-24 mg/dL) than with sitagliptin (-11 mg/dL) and saxagliptin (-3.6 mg/dL). Effectiveness was maintained in all age groups, provided disease duration was short (~5 to 6 years). Adverse effects were mild and transient and did not require treatment discontinuation. DPP-4 inhibitors are a viable option in patients with T2DM not adequately controlled by existing therapy. They demonstrate comparable efficacy to other antidiabetic medicines with regard to HbA1c reduction. The positive changes in the lipid profile make DPP-4 inhibitors a particularly interesting class of drugs; however, further studies are needed to confirm their true impact on cardiovascular risk in a real-world setting.
    Clinical Drug Investigation 05/2014;
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    ABSTRACT: Nomegestrol acetate (NOMAC)/17β-estradiol (E2) is a monophasic oral contraceptive that contains a progesterone-derived progestogen (NOMAC), and E2, a bio-identical estrogen. The primary objective of this thorough QT/QTc study was to investigate whether once-daily administration of therapeutic (2.5/1.5 mg) and supratherapeutic (12.5/7.5 mg) doses of NOMAC/E2 were associated with prolongation of the mean Fridericia-corrected QT (QTcF) interval in electrocardiograms at steady-state concentrations of NOMAC/E2 versus placebo. The co-primary objective was to establish assay sensitivity after a single dose of moxifloxacin (positive control). This was a randomized, double-blind, parallel-group trial comparing 2.5/1.5 mg of NOMAC/E2 (therapeutic dose), 12.5/7.5 mg of NOMAC/E2 (supratherapeutic dose), placebo, and moxifloxacin 400 mg. Double-blind study medication was administered from day -1 to 14. Healthy women aged 18-50 years were randomized. The largest time-matched mean QTcF difference compared with placebo for the therapeutic dose of NOMAC/E2 was 1.6 ms, with an upper limit (UL) of a one-sided 95 % confidence interval (CI) of 5.2 ms, and 3.1 ms with an UL 95 % CI of 7.0 ms for the supratherapeutic dose. The UL for the time-matched QTcF differences compared with placebo were below the 10 ms threshold defined in the ICH E14 guideline for all time points, both for the therapeutic and the supratherapeutic dose. For moxifloxacin, assay sensitivity was demonstrated. This thorough QT/QTc study showed that therapeutic and supratherapeutic doses of NOMAC/E2 were not associated with clinically relevant QTc interval prolongation in healthy women after a 2-week period of dosing.
    Clinical Drug Investigation 04/2014;
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    ABSTRACT: Dexmecamylamine (TC-5214) is a nicotinic channel modulator that was evaluated as a potential adjunct treatment to an antidepressant for patients with major depressive disorder. Dexmecamylamine is almost completely eliminated via the kidneys, with more than 90 % of a given dose excreted unchanged in urine. The aim of this study was to assess the single-dose pharmacokinetics of dexmecamylamine in subjects with various degrees of renal impairment and subjects undergoing hemodialysis. A single-dose, open-label, parallel-group study was conducted at two study centers in the USA. There were four treatment groups with eight subjects in each, receiving a single dose of dexmecamylamine 8 mg (subjects with normal renal function and mild renal impairment) or TC-5412 2 mg [subjects with moderate renal impairment and end-stage renal disease (ESRD)]. The pharmacokinetics of dexmecamylamine in plasma, urine, and dialysate were evaluated using non-compartmental analysis. The plasma pharmacokinetics of dexmecamylamine were influenced by renal function. The increase in dose-normalized area under the plasma concentration-time curve (AUC) was statistically significant with an approximately doubled exposure in subjects with moderate renal impairment compared with subjects with normal renal function. The maximum plasma concentration was not impacted by renal function. Plasma clearance of dexmecamylamine in ESRD subjects appeared negligible, with flat plasma concentration-time profiles. Hemodialysis had a relatively modest effect on reduction of dexmecamylamine plasma concentrations. There was no discernable relationship between renal clearance and urinary pH. Renal impairment increased the AUC, prolonged the elimination half-life, and decreased the clearance of dexmecamylamine following administration as a single oral dose. It is likely that renal function would need to be taken into account when setting the dose. Dexmecamylamine administration should be avoided or the dose significantly reduced in patients with severe renal impairment and ESRD.
    Clinical Drug Investigation 04/2014;
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    ABSTRACT: Icosapent ethyl (IPE) is a high-purity prescription form of eicosapentaenoic acid (EPA) ethyl ester approved to reduce triglyceride levels in patients with severe (≥5.65 mmol/L) hypertriglyceridemia. EPA, the active metabolite of IPE, is mainly metabolized via β-oxidation, and studies suggest that omega-3 fatty acids such as EPA may have antithrombotic effects. The objective of this study was to evaluate the effect of IPE on the pharmacokinetic and anticoagulation pharmacodynamics of warfarin, a substrate of cytochrome P450 2C9-mediated metabolism. Healthy adults received oral warfarin (25 mg) on day 1, oral IPE (4 g/day) on days 8-35, and co-administration on Day 29. Primary pharmacokinetic end points were area under the concentration-versus-time curve from zero to infinity (AUC0-∞) and maximum plasma concentration (C max) for R- and S-warfarin; pharmacodynamic end points were area under the international normalized ratio (INR) effect-time curve after the warfarin dose (AUCINR) and maximum INR (INRmax). Twenty-five subjects completed the study. AUC0-∞ and C max ratios of geometric means for both R- and S-warfarin following co-administration of warfarin with versus without IPE were within the 90 % confidence intervals of 0.80-1.25. AUCINR, INRmax, and ratios were also similar. IPE 4 g/day did not significantly change the single-dose AUC0-∞ or C max of R- and S-warfarin or the anticoagulation pharmacodynamics of warfarin when co-administered as racemic warfarin at 25 mg. Co-administration of these drugs was safe and well tolerated in this study of healthy adult subjects.
    Clinical Drug Investigation 04/2014;
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    ABSTRACT: A pharmacokinetic substudy was conducted within a phase 3 clinical trial that evaluated the efficacy and safety of two leuprolide acetate 3-month depot formulations in children with central precocious puberty (CPP), where the pharmacokinetics of leuprolide and the exposure-response relationship between leuprolide concentration and the probability of luteinizing hormone (LH) suppression were assessed. Children diagnosed with CPP (N = 42 in each dosing cohort), who were treatment naïve or previously treated, received a total of two intramuscular injections of either leuprolide acetate depot 11.25 or 30 mg formulations administered 3 months apart. Serial blood samples were collected for leuprolide concentration determination in a subset of subjects (N = 24 in each cohort). One-way analysis of covariance was used to assess dose proportionality. The probability of LH suppression (peak-stimulated LH concentrations <4 mIU/mL) exposure-response relationship was modelled using repeated measures logistic regression. The predicted probability of LH suppression and the corresponding 95 % confidence interval at the mean leuprolide concentration of each dose group and at each time of measurement were computed. Mean leuprolide concentrations between weeks 4 and 12 for 11.25 and 30 mg doses were relatively constant and dose proportional, with no accumulation of leuprolide upon repeated administration. Body weight and age were not found to be significant covariates on leuprolide pharmacokinetics. Higher leuprolide concentrations were associated with higher probability of LH suppression and both doses provided LH suppression levels <4 mIU/mL. Leuprolide pharmacokinetics were characterized for 11.25 and 30 mg 3-month depot injections. An exposure-response model was developed to link leuprolide concentrations and probability of peak-stimulated LH suppression.
    Clinical Drug Investigation 04/2014;
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    ABSTRACT: Adequate control of blood pressure in younger females is of crucial importance, because they are at higher risk of hypertensive target organ damage compared with males of similar age. In addition, female sex is a risk factor for adverse effects of antihypertensive drugs, especially dihydropyridines. This study set out to assess the incidence of adverse reactions during dihydropyridine use in a real-life clinical setting, focusing on the influence of female sex and age. The incidence of adverse reactions to dihydropyridine calcium channel blockers were investigated in 11,918 Japanese patients who participated in the Drug Event Monitoring project of the Japan Pharmaceutical Association conducted in Kumamoto prefecture. A multiple logistic regression analysis was used to determine the association between the incidence of adverse symptoms and female sex, with adjusted odds ratios (ORs) and 95 % confidence intervals (95 % CIs). Vasodilation-related adverse symptoms occurred significantly more often in females than in males (OR 1.87, 95 % CI 1.28-2.71, p = 0.001). Furthermore, among females only, the younger age group (<50 years) complained of vasodilation-related symptoms more frequently (OR 2.39, 95 % CI 1.02-5.59, p = 0.045) and the older age group (≥80 years) complained of vasodilation-related symptoms less frequently (OR 0.56, 95 % CI 0.33-0.95, p = 0.030) than the middle age group (50-79 years). To the best of our knowledge, this is the first report showing that younger females are at high risk for vasodilation-related adverse symptoms during dihydropyridine use in a real-life clinical setting. These results should be verified in clinical studies using larger samples of young patients and more parameters.
    Clinical Drug Investigation 04/2014;
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    ABSTRACT: Recent findings from randomized clinical trials indicate an improved patient adherence and blood pressure (BP) control by using fixed-dose combinations (FDCs) in the treatment of hypertension. The aim of the present study was to verify those data in a large real-world sample of hypertensive patients and to cross-check adherence evaluation performed by physicians and patients self-assessment. A European multi-center, prospective, 24-week, non-interventional study was conducted including 14,979 patients with essential hypertension and new treatment with olmesartan, amlodipine and hydrochlorothiazide as an FDC. Patients' adherence was measured using the Morisky Medication Adherence Scale (MMAS-8) and a non-standardized questionnaire was used by physicians and patients for self-assessment. The mean age of the patients was 63.9 ± 11.78 years and 46.5 % were women. One or more cardiovascular risk factors were present in 71.9 % of patients and 94.7 % had been treated for hypertension before study entry. Mean adherence to medication by MMAS-8 improved from 6.0 to 6.9 at study end. Corresponding improvements of adherence were seen on physicians' and patients' self-assessments throughout the study. Mean decrease of systolic/diastolic BP was 26.4/12.8 mmHg without a relevant difference between the MMAS-8 adherence levels. BP target achievement improved from 55.3 to 67.7 % in patients with low versus high adherence. The overall rate of patients with adverse drug reactions was very low (1.76 %) but more frequent in patients with low adherence. Our data confirm previous clinical trial data on the improvement of medication adherence by switching antihypertensive combination therapy to an FDC and a subsequent improvement in BP target achievement. An observed trend toward a reduction in adverse drug reactions needs to be further investigated in clinical trials.
    Clinical Drug Investigation 04/2014;
  • Clinical Drug Investigation 04/2014;
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    ABSTRACT: Although not designed for research purposes, medical charts can be a unique source for obtaining information on long-term adverse drug reactions. This study aimed to assess the availability of key information on paper-based patient medical records needed to detect long-term adverse reactions to antiretroviral therapy (ART). This is an ongoing historical cohort study carried out in three public HIV/AIDS referral centers in Belo Horizonte, Brazil. Medical charts of treatment-naïve HIV-infected adult patients initiating ART between 2001 and 2005 were reviewed for a follow-up period of up to 5 years after the first ART prescription. Descriptive analysis was performed by estimating the absolute and relative frequencies of selected variables. The Naranjo algorithm was employed to assess the availability of data on long-term adverse outcomes in medical charts. A total of 233 medical charts were eligible for study and 26.1 % contained at least one long-term adverse reaction, corresponding to 45 cases of dyslipidemia (19.3 %), 16 (6.9 %) of lipodystrophy and 5 of type 2 diabetes mellitus (2.1 %). Temporal relationship and ART switch could be better documented from medical charts. Information on reasons for ART switching and alternative causes for adverse reactions was very lacking. Specific tools should be developed and included in medical routines to improve adverse reaction reporting by physicians and other health professionals. This could be implemented simultaneously with the transition from paper to electronic medical charts in Brazil, facilitating the identification of long-term adverse reactions to antiretroviral drugs in epidemiological studies and in clinical practice.
    Clinical Drug Investigation 04/2014;
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    ABSTRACT: Levomilnacipran is a serotonin and norepinephrine reuptake inhibitor with greater potency for the reuptake inhibition of norepinephrine than of serotonin, approved in the USA for the treatment of major depressive disorder (MDD) in adults. A single-dose, open-label, parallel-group study was conducted to evaluate the effects of hepatic impairment on the pharmacokinetics of levomilnacipran in adults with mild, moderate, or severe hepatic impairment and normal controls receiving a 40 mg levomilnacipran extended-release (ER) capsule. The concentrations of levomilnacipran and its inactive metabolite, N-desethyl levomilnacipran, in plasma and urine were measured using liquid chromatography-tandem mass spectrometry methods. Pharmacokinetic parameters of levomilnacipran and N-desethyl levomilnacipran were derived and assessed. Safety parameters were assessed throughout the trial. No deaths, serious adverse events, or discontinuations due to adverse events occurred. The maximum plasma drug concentration (C max) and area under the plasma concentration-time curve from time zero to infinity (AUC∞) of levomilnacipran were 28 and 32 % higher, respectively, in participants with severe hepatic impairment than in healthy participants without a notable change in the t ½, whereas the C max and AUC∞ of N-desethyl levomilnacipran were 66 and 85 % lower, respectively, suggesting liver function has minimal impact on the overall exposure of levomilnacipran but plays a significant role in the formation of the metabolite. A single dose of levomilnacipran ER 40 mg was generally well-tolerated in participants with varying degrees of hepatic impairment and healthy controls. Therefore, dose adjustment for levomilnacipran is not necessary in adult MDD patients with impaired liver function.
    Clinical Drug Investigation 03/2014;

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