Home About us Contact
|
Home About us Contact | ||
|
|
||
Oral Placebo (oral + placebo)
Selected AbstractsA Double-Blind Comparison of OnabotulinumtoxinA (BOTOX®) and Topiramate (TOPAMAX®) for the Prophylactic Treatment of Chronic Migraine: A Pilot StudyHEADACHE, Issue 10 2009Ninan T. Mathew MD Background., There is a need for effective prophylactic therapy for chronic migraine (CM) that has minimal side effects. Objective., To compare the efficacy and safety of onabotulinumtoxinA (BOTOX®, Allergan, Inc., Irvine, CA) and topiramate (TOPAMAX®, Ortho-McNeil, Titusville, NJ) prophylactic treatment in patients with CM. Methods., In this single-center, double-blind trial, patients with CM received either onabotulinumtoxinA, maximum 200 units (U) at baseline and month 3 (100 U fixed-site and 100 U follow-the-pain), plus an oral placebo, or topiramate, 4-week titration to 100 mg/day with option for additional 4-week titration to 200 mg/day, plus placebo saline injections. OnabotulinumtoxinA or placebo saline injection was administered at baseline and month 3 only, while topiramate oral treatment or oral placebo was continued through the end of the study. The primary endpoint was treatment responder rate assessed using Physician Global Assessment 9-point scale (+4 = clearance of signs and symptoms and ,4 = very marked worsening [about 100% worse]). Secondary endpoints included the change from baseline in the number of headache (HA)/migraine days per month (HA diary), and HA disability measured using Headache Impact Test (HIT-6), HA diary, Migraine Disability Assessment (MIDAS) questionnaire, and Migraine Impact Questionnaire (MIQ). The overall study duration was approximately 10.5 months, which included a 4-week screening period and a 2-week optional final safety visit. Follow-up visits for assessments occurred at months 1, 3, 6, and 9. Adverse events (AEs) were documented. Results., Of 60 patients randomized to treatment (mean age, 36.8 ± 10.3 years; 90% female), 36 completed the study at the end of the 9 months of active treatment (onabotulinumtoxinA, 19/30 [63.3%]; topiramate, 17/30 [56.7%]). In the topiramate group, 7/29 (24.1%) discontinued study because of treatment-related AEs vs 2/26 (7.7%) in the onabotulinumtoxinA group. Between 68% and 83% of patients for both onabotulinumtoxinA and topiramate groups reported at least a slight (25%) improvement in migraine; response to treatment was assessed using Physician Global Assessment at months 1, 3, 6, and 9. Most patients in both groups reported moderate to marked improvements at all time points. No significant between-group differences were observed, except for marked improvement at month 9 (onabotulinumtoxinA, 27.3% vs topiramate, 60.9%, P = .0234, chi-square). In both groups, HA/migraine days decreased and MIDAS and HIT-6 scores improved. Patient-reported quality of life measures assessed using MIQ after treatment with onabotulinumtoxinA paralleled those seen after treatment with topiramate in most respects. At month 9, 40.9% and 42.9% of patients in the onabotulinumtoxinA and topiramate groups, respectively, reported ,50% reduction in HA/migraine days. Forty-one treatment-related AEs were reported in 18 onabotulinumtoxinA-treated patients vs 87 in 25 topiramate-treated patients, and 2.7% of patients in the onabotulinumtoxinA group and 24.1% of patients in the topiramate group reported AEs that required permanent discontinuation of study treatment. Conclusions., OnabotulinumtoxinA and topiramate demonstrated similar efficacy in the prophylactic treatment of CM. Patients receiving onabotulinumtoxinA had fewer AEs and discontinuations. [source] ALDH2 Status, Alcohol Expectancies, and Alcohol Response: Preliminary Evidence for a Mediation ModelALCOHOLISM, Issue 11 2001Denis M. McCarthy Background: A genetic variant in the alcohol-metabolizing enzyme (aldehyde dehydrogenase;ALDH2*2 allele), common in individuals of Asian heritage, has been associated with both physiologic response to alcohol and alcohol consumption. Prior research has also demonstrated that those with ALDH2*2 alleles have lower positive alcohol expectancies than those without these alleles. This preliminary study was designed to test whether the level of response to alcohol is the mechanism by which ALDH2 status may affect alcohol expectancies. Methods: Data were collected from 32 Asian American college students (14 women and 18 men). By use of a randomized, double-blind design, participants were administered oral placebo and alcohol at separate laboratory sessions. Data included blood tests to establish ALDH2 status, questionnaire measures of demographic information and alcohol expectancy, and several physiologic measures collected after placebo and alcohol administration. Results: ALDH2 status was related to alcohol response measures for both men and women. ALDH2 status was also related to tension reduction expectancies for women and to expectancies for cognitive behavioral impairment for men. In the male sample, the ALDH2/expectancy relationship was fully explained by the level of response to alcohol. Conclusions: These results represent a first step in understanding the mechanisms by which genetic factors, such as ALDH2 status, can affect alcohol-related learning. [source] The effects of midodrine on the natriuretic response to furosemide in cirrhotics with ascitesALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2010V. L. Misra Aliment Pharmacol Ther 2010; 32: 1044,1050 Summary Background, Resistance to loop diuretics is common in patients with ascites. Diminished glomerular filtration rate (GFR) is thought to mediate resistance to loop diuretics. Midodrine, a commonly used alpha-1 agonist, has been shown to improve GFR in non-azotemic patients with cirrhosis. Aim, To conduct a randomized, double-blind, placebo-controlled, cross-over study to test the hypothesis that midodrine significantly increases natriuretic response of IV furosemide in non-azotemic cirrhotics with ascites. Methods, All subjects participated in both phases, which were (i) furosemide IV infusion + oral midodrine 15 mg administered 30 min before furosemide (ii) furosemide IV infusion + oral placebo administered 30 min before furosemide. Primary outcomes were 6-h urine sodium excretion and 6-h total urine volume. Results, A total of 15 patients (men: 8; age: 52.7 ± 7.6 years; serum creatinine: 1.06 ± 0.2 mg/dL) were studied. Total 6-h urine sodium excretion was 109 ± 42 mmol in the furosemide + midodrine treatment phase and was not significantly different from that in the furosemide + placebo treatment phase (126 ± 69 mmol, P = 0.6). Similarly, mean 6-h total urine volume was not significantly different between two groups (1770 ± 262 mL vs. 1962 ± 170 mL, P = 0.25). Conclusions, Oral midodrine does not increase the natriuretic response to furosemide in non-azotemic cirrhotic patients with ascites. Orally administered midodrine does not increase natriuretic response to furosemide in non-azotemic cirrhotic patients with ascites. [source] CONTROLLED-RELEASE OXYCODONE RELIEVES MODERATE TO SEVERE PAIN IN A 3-MONTH STUDY OF PERSISTENT MODERATE TO SEVERE BACK PAINPAIN MEDICINE, Issue 2 2002Article first published online: 4 JUL 200 Patricia Richards, MD, PhD; Pinggao Zhang, PhD; Michael Friedman, PhD; Rahul Dhanda, PhD. (Purdue Pharma L.P.) Introduction: Opioids are frequently prescribed for management of persistent low back pain, however, efficacy has not been well documented, and concerns are that opioids may impair physical functioning. Objective: To compare controlled-release oxycodone (CRO) with placebo in controlling pain and to observe the effect of CRO on quality of life and functionality. Methods: A double-blind, randomized, placebo-controlled, parallel-group study of 3 months duration was conducted in 110 subjects (49 males, 61 females), mean age 48 years (19,80 years). Subjects had a 3- to 12-month history of moderate to severe persistent low back pain and were previously unresponsive to therapeutic doses of NSAIDs, and/or low dose combination opioid analgesics. At baseline 4% of subjects were on opioids, 39% on NSAIDs, and 57% both NSAIDs and opioids. Subjects were treated with 10 mg CRO tablet or 10 mg oral placebo q12h, titrated to stable pain control. Existing treatment regimens of acetaminophen, NSAIDs, or oral steroids were allowed to continue. The Brief Pain Inventory (BPI), the Roland Morris Functionality Questionnaire, and the MOS 36-Item Short-Form Health Survey (SF-36) were the measures of pain intensity, functionality, and quality of life. Treatments were compared using repeated measures ANCOVA with baseline value as covariate. Results: CRO treatment was significantly superior to placebo on the BPI average pain intensity and average percent pain relief scores overall (4.6 vs 5.4, P = .03, and 47.2 vs 36.3, P = .05, respectively). Fewer CRO subjects discontinued because of inadequate pain control (P < .001). No significant differences between treatments were observed in either Roland Morris or SF-36 scores. Common adverse events for CRO were nausea, constipation, somnolence, headache, and pruritus, consistent with opioid use. Conclusions: Three-month treatment with CRO provides significant pain relief for subjects with persistent moderate to severe back pain, without significantly impairing functionality and quality of life. The support of Purdue Pharma L.P. for this research project is gratefully acknowledged. [source] Comparison of the Effect of the Aromatase Inhibitor, Anastrazole, to the Antioestrogen, Tamoxifen Citrate, on Canine Prostate and SemenREPRODUCTION IN DOMESTIC ANIMALS, Issue 2009G Gonzalez Contents This study compared the efficiency of the aromatase inhibitor, anastrazole, with the antioestrogenic receptor blocker, tamoxifen, on normal (NRL) and hyperplastic prostate glands. Forty healthy dogs were classified as NRL (n = 18) or abnormal (ABN) with benign prostate hyperplasia (n = 22). The dogs were randomly assigned to one of the following six groups, treated for 60 days; oral placebo for normal (NRL-PLC; n = 6) and abnormal (ABN-PLC; n = 6), oral anastrazole 0.25,1 mg/day, for normal (NRL-ANZ, n = 6) and abnormal (ABN-ANZ, n = 8) and oral tamoxifen citrate 2.5,10 mg/day for normal (NRL-TMX; n = 6) and abnormal (ABN-TMX; n = 8) dogs. The dogs were evaluated before treatment and then monthly for 4 months. At the end of the treatment, the prostatic volume decreased by 28.5 ± 4.3%, 21.6 ± 6.3% and 0.7 ± 1.0% in the ABN-TMX, ABN-ANZ and ABN-PLC (p < 0.01), respectively. From then on, prostatic volume began to increase without reaching pre-treatment values at the end of the study. In the ABN animals, there were no differences for this parameter between ANZ and TMX treatment (p > 0.1), whereas in the NRL animals ANZ produced a less pronounced decrease (p < 0.05), libido, testicular consistency and scrotal diameter decreased during treatment in the TMX group (p > 0.05). These parameters and sperm volume, count, motility and morphological abnormalities remained unaltered throughout the study in the ANZ and PLC groups (p > 0.05). There were no haematological nor biochemical side effects. Anastrazole might offer a safe and effective alternative for the medical management of dogs with benign prostatic hyperplasia. [source] Ibudilast in healthy volunteers: safety, tolerability and pharmacokinetics with single and multiple dosesBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 6 2008Paul Rolan WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Ibudilast is an oral drug approved in Asia for asthma. , Tolerability of 10-mg regimens has been described previously. , Published pharmacokinetics (PK) are limited: single or 7-day repeat oral administration of 10 mg in healthy male Asian volunteers. WHAT THIS STUDY ADDS , Safety/tolerability and PK of a single 30-mg dose and a 30-mg twice daily (b.i.d.) 2-week regimen in male and female healthy volunteers. , Higher-dose regimens are relevant for testing in new neurological indications. , LC-MS/MS analytics for quantification of plasma and urine levels of ibudilast parent and its primary metabolite (6,7-dihydrodiol-ibudilast). AIMS To investigate the safety, tolerability and pharmacokinetics (PK) of ibudilast after a single-dose and a multiple-dose regimen. METHODS Healthy adult male (n = 9) and female (n = 9) volunteers were evaluated over a 17-day stay in a Phase 1 unit. Subjects were randomized 1 : 3 to either oral placebo or ibudilast at 30-mg single administration followed by 14 days of 30 mg b.i.d. Complete safety analyses were performed and, for PK, plasma and urine samples were analysed for ibudilast and its major metabolite. RESULTS Ibudilast was generally well tolerated. No serious adverse events occurred. Treatment-related adverse events included hyperhidrosis, headache and nausea. Two subjects discontinued after a few days at 30 mg b.i.d. because of vomiting. Although samples sizes were too small to rule out a sex difference, PK were similar in men and women. The mean half-life for ibudilast was 19 h and median Tmax was 4,6 h. Mean (SD) steady-state plasma Cmax and AUC0,24 were 60 (25) ng ml,1 and 1004 (303) ng h ml,1, respectively. Plasma levels of 6,7- dihydrodiol-ibudilast were approximately 30% of the parent. CONCLUSIONS Ibudilast is generally well tolerated in healthy adults when given as a single oral dose of 30 mg followed by 30 mg b.i.d. (60 mg day,1) for 14 days. Plasma PK reached steady state within 2 days of starting the b.i.d. regimen. Exposure to ibudilast was achieved of a magnitude comparable to that associated with efficacy in rat chronic pain models. [source] | ||||||||||