Ilya Petrou

GENEVA — Overweight and obese patients achieved significant weight loss and improved metabolic parameters using taranabant, according to interim results from a 2-year study.

Taranabant is a structurally distinct, highly selective cannabinoid-1 (CB-1) receptor inverse agonist under investigation for the treatment of obesity.

“With diet and exercise, treatment with taranabant 2 mg for 52 weeks was generally well tolerated and led to clinically meaningful weight loss in obese and overweight patients,” said Dr. Joe Proietto of the University of Melbourne, who presented the results at the 16th European Congress on Obesity. “Relative to taranabant dosed at 2 mg, the 4-mg and 6-mg doses were associated with slightly more weight loss, but at an increased incidence of adverse events.”

In a previous phase II study with taranabant dosed at 0.5, 2, 4, or 6 mg/day, a dose-dependent and clinically meaningful weight loss was seen in obese patients at 12 weeks, compared with placebo. This current ongoing 2-year phase III study was designed to evaluate the long-term efficacy and safety taranabant in overweight and obese patients. End points included changes in body weight, waist circumference, and serum lipids, and the proportion of subjects with metabolic syndrome.

After a 2-week single-blind placebo and diet run-in period, 2,502 overweight (body mass index greater than 25 kg/m

The researchers found that the least-squares mean changes from baseline in body weight were −2.6 kg, −6.6 kg, and −8.1 kg in patients receiving placebo, taranabant 2 mg, and taranabant 4 mg, respectively.

Compared with placebo, taranabant dosed at 2 and 4 mg showed significant improvement in waist circumference (−3.1%, −7.0%, and −7.5%, respectively) and a positive impact in changes in HDL cholesterol (7.0%, 13.2%, and 14.1%, respectively), triglycerides (4.0%, −3.1%, and −6.2%, respectively), and the proportion of patients with metabolic syndrome (47.3%, 36.0%, and 30.7%, respectively).

There were no significant changes seen in glucose metabolism—including fasting glucose, fasting insulin, or the quantitative insulin sensitivity check index measure of insulin sensitivity—or in blood pressure when compared with placebo.

After a year of diet and exercise, patients randomized to placebo showed a slight increase in triglycerides, for which Dr. Proietto had no conclusive explanation. Other studies also have shown slightly increased triglycerides, which tend to be fairly labile and can fluctuate in patients, according to Dr. Proietto.

Adverse events included gastrointestinal-related events in 28.5% of the placebo group and in 41.8% and 46.7% of the taranabant 2-mg and 4-mg groups, respectively. Psychiatric adverse events occurred in 20.4% of the placebo group and 28.3% and 40.2% of the taranabant 2-mg and 4-mg groups, respectively.

Dr. Proietto disclosed that he is a member of an advisory board for Merck & Co., which is developing taranabant. His institution participated in the current trial.

There was slightly more weight loss with higher doses of taranabant, but at an increased incidence of adverse events. DR. PROIETTO

GENEVA — Overweight and obese patients achieved significant weight loss and improved metabolic parameters using taranabant, according to interim results from a 2-year study.

Taranabant is a structurally distinct, highly selective cannabinoid-1 (CB-1) receptor inverse agonist under investigation for the treatment of obesity.

“With diet and exercise, treatment with taranabant 2 mg for 52 weeks was generally well tolerated and led to clinically meaningful weight loss in obese and overweight patients,” said Dr. Joe Proietto of the University of Melbourne, who presented the results at the 16th European Congress on Obesity. “Relative to taranabant dosed at 2 mg, the 4-mg and 6-mg doses were associated with slightly more weight loss, but at an increased incidence of adverse events.”

In a previous phase II study with taranabant dosed at 0.5, 2, 4, or 6 mg/day, a dose-dependent and clinically meaningful weight loss was seen in obese patients at 12 weeks, compared with placebo. This current ongoing 2-year phase III study was designed to evaluate the long-term efficacy and safety taranabant in overweight and obese patients. End points included changes in body weight, waist circumference, and serum lipids, and the proportion of subjects with metabolic syndrome.

After a 2-week single-blind placebo and diet run-in period, 2,502 overweight (body mass index greater than 25 kg/m

The researchers found that the least-squares mean changes from baseline in body weight were −2.6 kg, −6.6 kg, and −8.1 kg in patients receiving placebo, taranabant 2 mg, and taranabant 4 mg, respectively.

Compared with placebo, taranabant dosed at 2 and 4 mg showed significant improvement in waist circumference (−3.1%, −7.0%, and −7.5%, respectively) and a positive impact in changes in HDL cholesterol (7.0%, 13.2%, and 14.1%, respectively), triglycerides (4.0%, −3.1%, and −6.2%, respectively), and the proportion of patients with metabolic syndrome (47.3%, 36.0%, and 30.7%, respectively).

There were no significant changes seen in glucose metabolism—including fasting glucose, fasting insulin, or the quantitative insulin sensitivity check index measure of insulin sensitivity—or in blood pressure when compared with placebo.

After a year of diet and exercise, patients randomized to placebo showed a slight increase in triglycerides, for which Dr. Proietto had no conclusive explanation. Other studies also have shown slightly increased triglycerides, which tend to be fairly labile and can fluctuate in patients, according to Dr. Proietto.

Adverse events included gastrointestinal-related events in 28.5% of the placebo group and in 41.8% and 46.7% of the taranabant 2-mg and 4-mg groups, respectively. Psychiatric adverse events occurred in 20.4% of the placebo group and 28.3% and 40.2% of the taranabant 2-mg and 4-mg groups, respectively.

Dr. Proietto disclosed that he is a member of an advisory board for Merck & Co., which is developing taranabant. His institution participated in the current trial.

There was slightly more weight loss with higher doses of taranabant, but at an increased incidence of adverse events. DR. PROIETTO

GENEVA — Overweight and obese patients achieved significant weight loss and improved metabolic parameters using taranabant, according to interim results from a 2-year study.

Taranabant is a structurally distinct, highly selective cannabinoid-1 (CB-1) receptor inverse agonist under investigation for the treatment of obesity.

“With diet and exercise, treatment with taranabant 2 mg for 52 weeks was generally well tolerated and led to clinically meaningful weight loss in obese and overweight patients,” said Dr. Joe Proietto of the University of Melbourne, who presented the results at the 16th European Congress on Obesity. “Relative to taranabant dosed at 2 mg, the 4-mg and 6-mg doses were associated with slightly more weight loss, but at an increased incidence of adverse events.”

In a previous phase II study with taranabant dosed at 0.5, 2, 4, or 6 mg/day, a dose-dependent and clinically meaningful weight loss was seen in obese patients at 12 weeks, compared with placebo. This current ongoing 2-year phase III study was designed to evaluate the long-term efficacy and safety taranabant in overweight and obese patients. End points included changes in body weight, waist circumference, and serum lipids, and the proportion of subjects with metabolic syndrome.

After a 2-week single-blind placebo and diet run-in period, 2,502 overweight (body mass index greater than 25 kg/m

The researchers found that the least-squares mean changes from baseline in body weight were −2.6 kg, −6.6 kg, and −8.1 kg in patients receiving placebo, taranabant 2 mg, and taranabant 4 mg, respectively.

Compared with placebo, taranabant dosed at 2 and 4 mg showed significant improvement in waist circumference (−3.1%, −7.0%, and −7.5%, respectively) and a positive impact in changes in HDL cholesterol (7.0%, 13.2%, and 14.1%, respectively), triglycerides (4.0%, −3.1%, and −6.2%, respectively), and the proportion of patients with metabolic syndrome (47.3%, 36.0%, and 30.7%, respectively).

There were no significant changes seen in glucose metabolism—including fasting glucose, fasting insulin, or the quantitative insulin sensitivity check index measure of insulin sensitivity—or in blood pressure when compared with placebo.

After a year of diet and exercise, patients randomized to placebo showed a slight increase in triglycerides, for which Dr. Proietto had no conclusive explanation. Other studies also have shown slightly increased triglycerides, which tend to be fairly labile and can fluctuate in patients, according to Dr. Proietto.

Adverse events included gastrointestinal-related events in 28.5% of the placebo group and in 41.8% and 46.7% of the taranabant 2-mg and 4-mg groups, respectively. Psychiatric adverse events occurred in 20.4% of the placebo group and 28.3% and 40.2% of the taranabant 2-mg and 4-mg groups, respectively.

Dr. Proietto disclosed that he is a member of an advisory board for Merck & Co., which is developing taranabant. His institution participated in the current trial.

There was slightly more weight loss with higher doses of taranabant, but at an increased incidence of adverse events. DR. PROIETTO

GENEVA — A good night's sleep of 7–8 hours may be a key factor in staying slim, and any deviations from this ideal could cause weight gain, results of a 6-year prospective study suggest.

Of 276 adults who participated in the study, 31% had a weight gain of at least 5 kg during the follow-up period. Short-duration (5–6 hours) and long-duration (9–10 hours) sleepers were 35% and 25% more likely, respectively, to have a 5-kg weight gain, compared with those who slept for 7–8 hours.

“Both shorter and longer sleep duration times can predict higher body weight and fat gain in adults, independent of baseline weight or other covariates,” Jean-Philippe Chaput of Laval University, Quebec City, said at the 16th European Congress on Obesity. Sleep duration should be added to the list of determinants that contribute to weight gain and obesity, he noted.

The investigators evaluated the relationship between sleep duration and subsequent body weight and fat gain in the participants, who were aged 21–64 years. Changes in adiposity indices, including body mass index, waist circumference, percent body fat, and fat mass, were compared.

The risk of developing obesity was elevated for short- and long-duration sleepers, compared with average-duration sleepers, with a 27% and 21% increase in risk, respectively. The data were adjusted for covariates including resting metabolic rate, physical activity, and smoking habits.

Compared with those in the normal-duration sleep group, short and long sleepers had greater increases in waist circumference (58% and 47% more, respectively) and greater weight gain (1.8 kg and 1.5 kg, respectively).

According to Mr. Chaput, the most plausible explanation for the sleep and body weight association is an alteration of hormones, such as leptin and ghrelin. Short sleepers are characterized by low leptin levels and high ghrelin levels, suggesting that a positive caloric balance might occur which could lead to weight gain over time.

The researchers previously investigated the effect of sleep duration on weight in children, finding that short sleep duration increases the risk of overweight and obesity in this population as well.

“Furthermore, short sleep duration favors abdominal adiposity rather than total adiposity in children. This suggests the impact of short sleep duration might be more deleterious than previously thought,” Mr. Chaput said, adding that short sleep duration was the most important risk factor for obesity or overweight in children, followed by parental obesity, watching TV, and physical inactivity.

GENEVA — A good night's sleep of 7–8 hours may be a key factor in staying slim, and any deviations from this ideal could cause weight gain, results of a 6-year prospective study suggest.

Of 276 adults who participated in the study, 31% had a weight gain of at least 5 kg during the follow-up period. Short-duration (5–6 hours) and long-duration (9–10 hours) sleepers were 35% and 25% more likely, respectively, to have a 5-kg weight gain, compared with those who slept for 7–8 hours.

“Both shorter and longer sleep duration times can predict higher body weight and fat gain in adults, independent of baseline weight or other covariates,” Jean-Philippe Chaput of Laval University, Quebec City, said at the 16th European Congress on Obesity. Sleep duration should be added to the list of determinants that contribute to weight gain and obesity, he noted.

The investigators evaluated the relationship between sleep duration and subsequent body weight and fat gain in the participants, who were aged 21–64 years. Changes in adiposity indices, including body mass index, waist circumference, percent body fat, and fat mass, were compared.

The risk of developing obesity was elevated for short- and long-duration sleepers, compared with average-duration sleepers, with a 27% and 21% increase in risk, respectively. The data were adjusted for covariates including resting metabolic rate, physical activity, and smoking habits.

Compared with those in the normal-duration sleep group, short and long sleepers had greater increases in waist circumference (58% and 47% more, respectively) and greater weight gain (1.8 kg and 1.5 kg, respectively).

According to Mr. Chaput, the most plausible explanation for the sleep and body weight association is an alteration of hormones, such as leptin and ghrelin. Short sleepers are characterized by low leptin levels and high ghrelin levels, suggesting that a positive caloric balance might occur which could lead to weight gain over time.

The researchers previously investigated the effect of sleep duration on weight in children, finding that short sleep duration increases the risk of overweight and obesity in this population as well.

“Furthermore, short sleep duration favors abdominal adiposity rather than total adiposity in children. This suggests the impact of short sleep duration might be more deleterious than previously thought,” Mr. Chaput said, adding that short sleep duration was the most important risk factor for obesity or overweight in children, followed by parental obesity, watching TV, and physical inactivity.

GENEVA — A good night's sleep of 7–8 hours may be a key factor in staying slim, and any deviations from this ideal could cause weight gain, results of a 6-year prospective study suggest.

Of 276 adults who participated in the study, 31% had a weight gain of at least 5 kg during the follow-up period. Short-duration (5–6 hours) and long-duration (9–10 hours) sleepers were 35% and 25% more likely, respectively, to have a 5-kg weight gain, compared with those who slept for 7–8 hours.

“Both shorter and longer sleep duration times can predict higher body weight and fat gain in adults, independent of baseline weight or other covariates,” Jean-Philippe Chaput of Laval University, Quebec City, said at the 16th European Congress on Obesity. Sleep duration should be added to the list of determinants that contribute to weight gain and obesity, he noted.

The investigators evaluated the relationship between sleep duration and subsequent body weight and fat gain in the participants, who were aged 21–64 years. Changes in adiposity indices, including body mass index, waist circumference, percent body fat, and fat mass, were compared.

The risk of developing obesity was elevated for short- and long-duration sleepers, compared with average-duration sleepers, with a 27% and 21% increase in risk, respectively. The data were adjusted for covariates including resting metabolic rate, physical activity, and smoking habits.

Compared with those in the normal-duration sleep group, short and long sleepers had greater increases in waist circumference (58% and 47% more, respectively) and greater weight gain (1.8 kg and 1.5 kg, respectively).

According to Mr. Chaput, the most plausible explanation for the sleep and body weight association is an alteration of hormones, such as leptin and ghrelin. Short sleepers are characterized by low leptin levels and high ghrelin levels, suggesting that a positive caloric balance might occur which could lead to weight gain over time.

The researchers previously investigated the effect of sleep duration on weight in children, finding that short sleep duration increases the risk of overweight and obesity in this population as well.

“Furthermore, short sleep duration favors abdominal adiposity rather than total adiposity in children. This suggests the impact of short sleep duration might be more deleterious than previously thought,” Mr. Chaput said, adding that short sleep duration was the most important risk factor for obesity or overweight in children, followed by parental obesity, watching TV, and physical inactivity.

Four months after receiving one dose of the varicella vaccine only 76% of 148 children showed evidence of seroconversion, suggesting that many pediatric cases of varicella are caused by primary immunization failure, investigators have reported.

"The present findings … strongly support the use of a second dose of vaccine for all children without a history of disease," and the second dose should be given within months, rather than years, of the first, the researchers wrote.

This approach "will probably prevent not only the current phenomenon of isolated outbreaks of breakthrough disease but a subsequent epidemic of serious varicella in vaccinated but unprotected adults," wrote Dr. David E. Michalik of the division of pediatric infectious Diseases at Columbia University Medical Center, New York, and his colleagues (J. Infect. Dis. 2008;197:944–9).

The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention recommends that a second dose of varicella vaccine be administered routinely to children. The second dose can be given as soon as 3 months after the first dose.

Writing in an accompanying editorial, Dr. Eugene D. Shapiro of the Yale Center for Clinical Investigation at Yale University, New Haven, Conn., pointed out that the first and second doses of the varicella vaccine are sometimes given at the same time as the MMR vaccine via a combined MMR-varicella (MMR-V) vaccine at 12–15 months and again at 4–6 years.

"If the substantial number of cases of breakthrough varicella is due to primary, rather than secondary, vaccine failure, this timing for the second dose risks leaving a substantial number of children susceptible for several years until they receive the second dose," he wrote (J. Infect. Dis. 2008;197:935–7).

Dr. Michalik and his associates defined primary vaccine failure as the inability to mount a protective immune response after receiving a single dose of vaccine; secondary failure occurred when the demonstrable immune response to vaccination gradually waned over a long period of time.

The researchers conducted the multicenter study to ascertain whether recent reports of breakthrough varicella might represent the higher than expected rates of primary vaccine failure.

Using fluorescent antibody membrane antigen (FAMA) assay, Dr. Michalik and his associates studied the varicella zoster virus (VZV) antibody titers in 148 healthy immunized children before and after they had received one 0.5-mL dose of varicella vaccine. A total of 76% had seroconversion, but 24% showed no detectable VZV FAMA antibodies.

FAMA is considered the preferred method for assessment technique and has a high sensitivity and specificity for VZV antibodies. The seroconversion rates found in this study are significantly lower than those found in other studies (86%–96%) in which flagellar antigen enzyme-linked immunosorbent assay (GP ELISA) was used. The authors noted that the GP ELISA assay can cause false-positive results to occur, which can likely lead to overestimations of the rate of seroconversion.

The median age of participants was 12.5 months, and serum samples were obtained an average of 4 months post vaccination.

In his editorial, Dr. Shapiro stressed that the optimal use of this "effective vaccine" still needs to be determined.

"Because of the limited and conflicting data on which to base recommendations for policy, it is important to obtain additional data to try to clarify whether most breakthrough cases of varicella are due to primary or secondary vaccine failure. The immunogenicity of both monovalent varicella vaccine and of MMR-V vaccine … should be assessed by directly comparing the results of GP ELISA and FAMA assays in the same samples," Dr. Shapiro said.

Four months after receiving one dose of the varicella vaccine only 76% of 148 children showed evidence of seroconversion, suggesting that many pediatric cases of varicella are caused by primary immunization failure, investigators have reported.

"The present findings … strongly support the use of a second dose of vaccine for all children without a history of disease," and the second dose should be given within months, rather than years, of the first, the researchers wrote.

This approach "will probably prevent not only the current phenomenon of isolated outbreaks of breakthrough disease but a subsequent epidemic of serious varicella in vaccinated but unprotected adults," wrote Dr. David E. Michalik of the division of pediatric infectious Diseases at Columbia University Medical Center, New York, and his colleagues (J. Infect. Dis. 2008;197:944–9).

The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention recommends that a second dose of varicella vaccine be administered routinely to children. The second dose can be given as soon as 3 months after the first dose.

Writing in an accompanying editorial, Dr. Eugene D. Shapiro of the Yale Center for Clinical Investigation at Yale University, New Haven, Conn., pointed out that the first and second doses of the varicella vaccine are sometimes given at the same time as the MMR vaccine via a combined MMR-varicella (MMR-V) vaccine at 12–15 months and again at 4–6 years.

"If the substantial number of cases of breakthrough varicella is due to primary, rather than secondary, vaccine failure, this timing for the second dose risks leaving a substantial number of children susceptible for several years until they receive the second dose," he wrote (J. Infect. Dis. 2008;197:935–7).

Dr. Michalik and his associates defined primary vaccine failure as the inability to mount a protective immune response after receiving a single dose of vaccine; secondary failure occurred when the demonstrable immune response to vaccination gradually waned over a long period of time.

The researchers conducted the multicenter study to ascertain whether recent reports of breakthrough varicella might represent the higher than expected rates of primary vaccine failure.

Using fluorescent antibody membrane antigen (FAMA) assay, Dr. Michalik and his associates studied the varicella zoster virus (VZV) antibody titers in 148 healthy immunized children before and after they had received one 0.5-mL dose of varicella vaccine. A total of 76% had seroconversion, but 24% showed no detectable VZV FAMA antibodies.

FAMA is considered the preferred method for assessment technique and has a high sensitivity and specificity for VZV antibodies. The seroconversion rates found in this study are significantly lower than those found in other studies (86%–96%) in which flagellar antigen enzyme-linked immunosorbent assay (GP ELISA) was used. The authors noted that the GP ELISA assay can cause false-positive results to occur, which can likely lead to overestimations of the rate of seroconversion.

The median age of participants was 12.5 months, and serum samples were obtained an average of 4 months post vaccination.

In his editorial, Dr. Shapiro stressed that the optimal use of this "effective vaccine" still needs to be determined.

"Because of the limited and conflicting data on which to base recommendations for policy, it is important to obtain additional data to try to clarify whether most breakthrough cases of varicella are due to primary or secondary vaccine failure. The immunogenicity of both monovalent varicella vaccine and of MMR-V vaccine … should be assessed by directly comparing the results of GP ELISA and FAMA assays in the same samples," Dr. Shapiro said.

Four months after receiving one dose of the varicella vaccine only 76% of 148 children showed evidence of seroconversion, suggesting that many pediatric cases of varicella are caused by primary immunization failure, investigators have reported.

"The present findings … strongly support the use of a second dose of vaccine for all children without a history of disease," and the second dose should be given within months, rather than years, of the first, the researchers wrote.

This approach "will probably prevent not only the current phenomenon of isolated outbreaks of breakthrough disease but a subsequent epidemic of serious varicella in vaccinated but unprotected adults," wrote Dr. David E. Michalik of the division of pediatric infectious Diseases at Columbia University Medical Center, New York, and his colleagues (J. Infect. Dis. 2008;197:944–9).

The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention recommends that a second dose of varicella vaccine be administered routinely to children. The second dose can be given as soon as 3 months after the first dose.

Writing in an accompanying editorial, Dr. Eugene D. Shapiro of the Yale Center for Clinical Investigation at Yale University, New Haven, Conn., pointed out that the first and second doses of the varicella vaccine are sometimes given at the same time as the MMR vaccine via a combined MMR-varicella (MMR-V) vaccine at 12–15 months and again at 4–6 years.

"If the substantial number of cases of breakthrough varicella is due to primary, rather than secondary, vaccine failure, this timing for the second dose risks leaving a substantial number of children susceptible for several years until they receive the second dose," he wrote (J. Infect. Dis. 2008;197:935–7).

Dr. Michalik and his associates defined primary vaccine failure as the inability to mount a protective immune response after receiving a single dose of vaccine; secondary failure occurred when the demonstrable immune response to vaccination gradually waned over a long period of time.

The researchers conducted the multicenter study to ascertain whether recent reports of breakthrough varicella might represent the higher than expected rates of primary vaccine failure.

Using fluorescent antibody membrane antigen (FAMA) assay, Dr. Michalik and his associates studied the varicella zoster virus (VZV) antibody titers in 148 healthy immunized children before and after they had received one 0.5-mL dose of varicella vaccine. A total of 76% had seroconversion, but 24% showed no detectable VZV FAMA antibodies.

FAMA is considered the preferred method for assessment technique and has a high sensitivity and specificity for VZV antibodies. The seroconversion rates found in this study are significantly lower than those found in other studies (86%–96%) in which flagellar antigen enzyme-linked immunosorbent assay (GP ELISA) was used. The authors noted that the GP ELISA assay can cause false-positive results to occur, which can likely lead to overestimations of the rate of seroconversion.

The median age of participants was 12.5 months, and serum samples were obtained an average of 4 months post vaccination.

In his editorial, Dr. Shapiro stressed that the optimal use of this "effective vaccine" still needs to be determined.

"Because of the limited and conflicting data on which to base recommendations for policy, it is important to obtain additional data to try to clarify whether most breakthrough cases of varicella are due to primary or secondary vaccine failure. The immunogenicity of both monovalent varicella vaccine and of MMR-V vaccine … should be assessed by directly comparing the results of GP ELISA and FAMA assays in the same samples," Dr. Shapiro said.