/publications/issue/2012/January2012/Outlook-Clinical-Trials

Outlook: Clinical Trials

Author: Michele Reed, PharmD


LANSOPRAZOlE FOR ASTHMA SYMPTOM REDUCTION 

Arecent randomized, masked, placebo-controlled, parallel clinical trial compared lansoprazole with placebo in children with poor asthma control who were receiving inhaled corti- costeroid treatment.1

Study subjects were randomized to receive either lansoprazole (n = 149) or placebo (n = 157). Subjects in the lanso- prazole group weighing less than 30 kg received 15 mg per day and subjects weighing 30 kg or more received 30 mg per day. The primary end point was change in Asthma Control Questionnaire (ACQ) score. Secondary end points included lung function measures, asth- ma-related quality of life, and episodes of poor asthma control.

Results showed that the mean differ- ence in change (lansoprazole minus pla- cebo) in the ACQ score was 0.2 units (95% confidence interval [CI], 0.0-0.3 units). There were no statistically significant dif- ferences in the mean difference in change for forced expiratory volume in the first second (0.0 L; 95% CI, -0.1 to 0.1 L), asth- ma-related quality of life (-0.1; 95% CI, -0.3 to 0.1), or rate of episodes of poor asthma control (relative risk, 1.2; 95% CI, 0.9-1.5). Additionally, it was observed that children in the lansoprazole group reported more respiratory infections.

The authors concluded that in the study population, lansoprazole did not show a clinical benefit compared with placebo, and it was associated with increased adverse events.


EFFECT OF ARB THERAPY ON INSULIN SENSITIVITY AND ENDOTHELIAL FUNCTION 

In a recent randomized, double-blind, parallel, placebo-controlled multicenter trial, investigators evaluated effects of angiotensin receptor blocker (ARB) therapy on insulin sensitivity and endothelial function.2 Study subjects (n = 53) with stage I hypertension, abdominal obesity, and impaired fasting glucose were randomized to receive losartan 100 mg per day or placebo. Insulin sensitiv- ity was measured using the hyperinsulinemic-euglycemic clamp technique and endothelial function was measured using reactive hyperemia-peripheral arterial tonometry (RH-PAT).

Results showed that ARB therapy did not alter insulin sensitivity (5.2 [2.7] pre-treatment and 4.6 [1.6] post-treatment) compared with placebo therapy (6.1 [2.9] pre-treatment and 5.3 [2.7] post-treatment; P value not significant). Additionally, ARB therapy did not change endothelial function (RH-PAT, 2.15 [0.7] pre-treatment and 2.11 [0.7] post-treatment) compared with placebo therapy (RH-PAT, 1.81 [0.5] pre-treatment and 1.76 [0.7] post-treatment; P value not significant). Study investigators concluded that ARB therapy did not alter peripheral insulin sensitivity or endothelial function in this cohort of patients.


QNASL FOR ALLERGIC RHINITIS 

At the 2012 American Academy of Allergy, Asthma & Immun- ology (AAAAI) Annual Meeting in Orlando, Florida, investiga- tors presented positive findings from phase 3 clinical studies of QNASL (beclomethasone dipropionate [BDP]) Nasal Aerosol.

In a long-term (52-week), double-blind, placebo-controlled, par- allel-group study, patients (n = 529) with perennial allergic rhinitis 12 years and older were randomized to receive once-daily treat- ment with QNASL 320 mcg or placebo. Primary end point results showed that the QNASL group experienced a significant (P <.001) change from baseline weekly averages of the subject-reported 24-hour reflective nasal symptom scores (rTNSS) over the first 30 weeks of the treatment period.

Additionally, 52-week treatment data reported at the AAAAI meeting further demonstrated the safety and efficacy profile of QNASL treatment by showing significantly greater improve- ments from baseline over a 24-hour period in both rTNSS (-1.09 [95% CI: -1.6, -0.6], P <.001) and instantaneous nasal symptom scores (-1.10 [95% CI: -1.6, -0.6]; P <.001) compared with placebo. QNASL was also shown to improve quality of life as assessed by the Rhinoconjunctivitis Quality of Life Questionnaire (-0.58 [95% CI: -0.9, -0.2]; P = .001) compared with placebo. QNASL at 320 mcg/ day was not associated with hypothalamic-pituitary-adrenal axis suppression in adult and adolescent subjects with PAR.

The most commonly reported adverse events (≥5% of subjects) were nasopharyngitis, epistaxis, upper respiratory tract infection, sinusitis, and headache, with epistaxis occurring more frequently in the QNASL group compared with placebo.


EFFICACY RESULTS OF AN HSV VACCINE TRIAL 

Arandomized, double-blind, efficacy field trial of an investi- gational vaccine involving women (n = 8323) aged 18 to 30 years who were negative for antibodies to herpes simplex virus type 1 (HSV-1) and HSV-2 was recently conducted.4

Study subjects were randomized to receive either the inves- tigational vaccine, consisting of 20 mcg of glycoprotein D from HSV-2 with alum and 3-O-deacylated monophosphoryl lipid A as an adjuvant or the hepatitis A vaccine, at a dose of 720 enzyme- linked immunosorbent assay units. The primary end point was occurrence of genital herpes disease due to either HSV-1 or HSV-2 from month 2 (1 month after dose 2) through month 20.

Results showed that, overall, the HSV vaccine efficacy was 20% (95% CI, -29 to 50) against genital herpes disease. Efficacy against HSV-1 genital disease was 58% (95% CI, 12 to 80). Vaccine effi- cacy against HSV-1 infection (with or without disease) was 35% (95% CI, 13 to 52), but efficacy against HSV-2 infection was not observed (-8%; 95% CI, -59 to 26).

Investigators concluded that the investigational vaccine was effective in preventing HSV-1 genital disease and infection but not in preventing HSV-2 disease or infection.


Dr. Reed received her doctor of pharmacy degree from the University of the Sciences in Philadelphia, Pennsylvania, and currently works as a medical editor in the greater Philadelphia area.


References

1. Writing Committee for the American Lung Association Asthma Clinical Research Centers, et al. Lansoprazole for children with poorly controlled asthma: a randomized controlled trial. JAMA. 2012;307(4):373-381.

2. Perlstein TS, Henry RR, Mather KJ, et al. Effect of angiotensin receptor blockade on insulin sensitivity and endothelial function in abdominally obese hypertensive patients with impaired fasting glucose. Clin Sci (Lond). 2012;122(4):193-202.

3. Lok AS, Gardiner DF, Lawitz E, et al. Preliminary study of two antiviral agents for hepatitis C genotype 1. N Engl J Med. 2012;366(3):216-224.

4. Belshe RB, Leone PA, Bernstein DI, et al. Efficacy results of a trial of a herpes simplex vaccine. N Engl J Med. 2012;366(1):34-43.