Major Finding: The proportions of patients achieving a meaningful change in weight-related quality of life ranged from 30%-36% with placebo, 37%-52% with the lower phentermine/topiramate dose, and 49%-52% with the higher dose.
Data Source: One randomized study (EQUIP) enrolled 1,267 subjects with BMIs of 35 or greater. The other randomized study (CONQUER) enrolled 2,487 patients who had BMIs of 27-45 plus two or more comorbidities.
Disclosures: All studies were funded by Vivus. Dr. Kolotkin and Ms. Rueger reported having no further disclosures.
LAS VEGAS – The investigational, controlled-release phentermine/topiramate combination produced significant weight loss that was associated with significantly improved quality of life in two studies of overweight and obese individuals.
Vivus Inc., which sponsored the studies, is developing the once-daily oral, controlled-release formulation of low-dose phentermine plus topiramate under the name Qnexa. Designed to decrease appetite and increase satiety, the combination treatment has completed phase III clinical trials for the treatment of obesity and is currently under evaluation by the Food and Drug Administration for that indication. It also is in phase II trials for the treatment of type 2 diabetes and obstructive sleep apnea, according to a company statement.
Ronette L. Kolotkin, Ph.D., summarized the 56-week weight loss data at the meeting and presented new findings on quality of life from two phase III, double-blind, placebo-controlled trials. One study (EQUIP) enrolled 1,267 subjects with body mass indexes of 35 kg/m
In the EQUIP trial, subjects were randomized to 3.75 mg phentermine/23 mg topiramate, 15 mg phentermine/92 mg topiramate, or placebo. They were mostly women (83%), with a mean age of 43 years and mean BMI of 42. Among those who completed 56 weeks of treatment, the percentage of weight loss was 3% for placebo, 7% for the lower dose, and 15% for the higher dose. In the intent-to-treat (ITT) analysis with the last observation carried forward (LOCF), the weight loss percentages were 2%, 5%, and 11%, respectively, said Dr. Kolotkin, a clinical psychologist, researcher, and consultant with Obesity and Quality of Life Consulting, Durham, N.C.
In the CONQUER trial, two-thirds of the patients were women, with a mean age of 51 years and a mean BMI of 37. They were randomized to 7.5 mg phentermine/46 mg topiramate, 15 mg phentermine/92 mg topiramate, or placebo. At 56 weeks, the completers had lost 2% of their body weight with placebo, 11% with the lower dose, and 13% with the higher dose. In the ITT/LOCF analysis, the weight loss percentages were 1%, 8%, and 10%, respectively. In both studies, weight loss was statistically significant for both drug doses but not for placebo, Dr. Kolotkin said.
Two measures were used to assess health-related quality of life (HRQOL). One, the Impact of Weight on Quality of Life–Lite (IWQOL-Lite), is a 31-item survey, each beginning with the phrase “Because of my weight…” with five possible responses ranging from “Never true” to “Always true.” Domains include physical function (“…I have trouble tying my shoe”), self-esteem (“I'm afraid of being rejected”), sexual life (“I do not enjoy sexual activity”), public distress (“I experience ridicule, teasing, etc.”), and work (“I am less productive than I could be”). Scoring is on a 0-100 scale, with a higher score signifying better HRQOL.
The other measure, the Study Short Form–36 (SF-36), assesses general HRQOL with a 36-item survey pertaining to physical and mental/psychosocial health, each with four health domains. Scoring is also on a 0-100 scale, with higher being better.
At 56 weeks in the ITT-LOCF analysis, IWQOL score changes were significantly better for both treatment groups than for placebo. With the higher dose, score increases ranged from 7 for work to 16 for self-esteem in EQUIP and from 8 for public distress to 16 for self-esteem in CONQUER.
On the SF-36, in CONQUER there were statistically significant increases from baseline to 56 weeks in the areas of physical functioning, physical role functioning, bodily pain, general health, vitality, and the overall physical component summary score. However, changes in the overall mental component, social functioning, emotional role functioning, and mental health were not significant, Dr. Kolotkin reported.
Further evaluation assessed the degree to which the changes were meaningful, with the definition of “meaningful” on the IWQOL-Lite total score as an increase of 8-12 points, depending on score severity at baseline (J. Clin. Epidemiol. 2004;57:1153-60).
In EQUIP, the proportions of patients achieving a meaningful change in weight-related quality of life were 30% with placebo, 37% with the lower phentermine/topiramate dose, and 49% with the higher dose.
In CONQUER, meaningful improvement on IWQOL-Lite occurred in 36% of the placebo patients, compared with 52% of each of the two doses of phentermine/topiramate. Similar results in CONQUER were seen with the SF-36, for which meaningful improvement was defined as an increase of 2.5 or more points. Those percentages were 36% for placebo, 55% for the lower dose, and 53% for the higher dose, she reported.