Pharmacokinetic Comparison of Multiple Formulations of Topiramate and Phentermine in Obese Adults

Vivus

Status and phase: Completed; Phase 1

Conditions: Obesity

Treatments: Drug: phentermine; Drug: topiramate

Study type: Interventional

Funder types: Industry

Identifiers

NCT00518466

OB-102 / AA42851

Details and patient eligibility

About

The primary objective of this study is to describe the single- and multiple-dose pharmacokinetic profiles of two novel formulations of topiramate and commercially available immediate release topiramate, all dosed with immediate release phentermine.

Enrollment: 64 patients

Sex: All

Ages: 19 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Obese adults
• Body mass index between 30.0 and 42.0 kg/m2 (inclusive)
• Medically healthy with no clinically significant results of screening exams

Exclusion criteria

• History or presence of significant cardiovascular, pulmonary, hepatic, renal, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease
• History of glaucoma or increased intraocular pressure
• History of kidney stones
• Cholelithiasis or cholecystitis within 6 months
• Cardiovascular event within 6 months
• Obesity of known genetic or endocrine origin
• Recent weight instability
• Use of Very Low Calorie diet or participation in organized weight loss program within 3 months
• Systolic blood pressure > 150 or diastolic > 95 mm Hg
• Positive urine drug or alcohol screen
• Positive serology for HIV, HBV, or HCV
• History of alcoholism or drug abuse
• History of significant psychiatric disease, current depression of moderate or greater severity, any history of suicidal ideation
• Hypersensitivity to study drug or related compounds
• Use of prescription or OTC medication other than hormonal contraceptive within 14 days prior to first dosing with study drug
• Blood donation or significant blood loss within 56 days or plasma donation within 7 days prior to first dosing with study drug
• Women who are pregnant or lactating
• Hemoglobin < 12 g/dL
• Use of tobacco or nicotine-containing products within 6 months

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

64 participants in 4 patient groups

treatment 1

Experimental group

Description:

One 7.5 mg phentermine hydrochloride IR capsule and two 25 mg topiramate MR capsules at Hour 0 on Day 1 of Period 1. One 7.5 mg phentermine hydrochloride IR capsule and one 25 mg topiramate MR capsule at Hour 0 on Days 1, 2, and 3 of Period 2. One 7.5 mg phentermine hydrochloride IR capsule and two 25 mg topiramate MR capsules at Hour 0 on Days 4 - 21 of Period 2.

Treatment:

Drug: phentermine

Drug: phentermine

Drug: topiramate

Drug: topiramate

treatment 2

Experimental group

Description:

Two 7.5 mg phentermine hydrochloride IR capsules and four 25 mg topiramate MR capsules at Hour 0 on Day 1 of Period 1. One 7.5 mg phentermine hydrochloride IR capsule and one 25 mg topiramate MR capsule at Hour 0 on Days 1, 2, and 3 of Period 2. One 7.5 mg phentermine hydrochloride IR capsules and two 25 mg topiramate MR capsules at Hour 0 on Days 4, 5, and 6 of Period 2. Two 7.5 mg phentermine hydrochloride IR capsules (Cardinal) and three 25 mg topiramate MR capsules at Hour 0 on Days 7, 8, and 9 of Period 2. Two 7.5 mg phentermine hydrochloride IR capsules and four 25 mg topiramate MR capsules at Hour 0 on Days 10 - 21 of Period 2.

Treatment:

Drug: phentermine

Drug: phentermine

Drug: topiramate

Drug: topiramate

treatment 3

Experimental group

Description:

Two 7.5 mg phentermine hydrochloride IR capsules and four 25 mg topiramate MR capsules at Hour 0 on Day 1 of Period 1. One 7.5 mg phentermine hydrochloride IR capsule and one 25 mg topiramate MR capsule at Hour 0 on Days 1, 2, and 3 of Period 2. Two 7.5 mg phentermine hydrochloride IR capsules and two 25 mg topiramate MR capsule at Hour 0 on Days 4, 5, and 6 of Period 2. Two 7.5 mg phentermine hydrochloride IR capsules and three 25 mg topiramate MR capsules at Hour 0 on Days 7, 8, and 9 of Period 2. Two 7.5 mg phentermine hydrochloride IR capsules and four 25 mg topiramate MR capsules at Hour 0 on Days 10 - 21 of Period 2.

Treatment:

Drug: phentermine

Drug: phentermine

Drug: topiramate

Drug: topiramate

treatment 4

Experimental group

Description:

Half of a 37.5 mg phentermine hydrochloride IR tablet and one 100 mg topiramate IR tablet at Hour 0 on Day 1 of Period 1. One 7.5 mg phentermine hydrochloride IR capsule and one 25 mg topiramate IR tablet at Hour 0 on Days 1, 2, and 3 of Period 2. Half of a 37.5 mg phentermine hydrochloride IR tablet and two 25 mg topiramate IR tablets at Hour 0 on Days 4, 5, and 6 of Period 2. Half of a 37.5 mg phentermine hydrochloride IR tablet and three 25 mg topiramate IR tablets at Hour 0 on Days 7, 8, and 9 of Period 2. Half of a 37.5 mg phentermine hydrochloride IR tablet and one 100 mg topiramate IR tablet at Hour 0 on Days 10 - 21 of Period 2.

Treatment:

Drug: phentermine

Drug: phentermine

Drug: topiramate

Drug: topiramate