Clinical Trials

Clinical Trials: A Practical Guide ■❚❙❘Table 1. A summary of the key features of two example crossover studies.Study 1 Study 2Design 2 × 2 crossover 2 × 2 crossoverObjective Bioequivalence evaluation Efficacy assessmentEndpoint Pharmacokinetic parameters Plasma concentration of activated protein C(AUC 0–t, AUC 0–∞, C max, T max, T 1/2, and λ)Treatment A 500 mg Cefuzime tablets 150 mg levonorgestrel and 30 mg ethinylestradiolTreatment B 500 mg Zinnat tablets 150 mg desogestrel and 30 mg ethinylestradiolSequence 1 AB ABSequence 2 BA BAPeriod 1 1 day 2 consecutive menstrual cyclesPeriod 2 1 day 2 consecutive menstrual cyclesWashout period 1 week 2 consecutive menstrual cyclesSample size 24 subjects 33 subjectsConclusion Bioequivalence between A and B Lower efficacy of B than AExample study 2: Low-dose oral contraceptives and acquiredresistance to activated protein C: a randomized crossover study [2]A randomized crossover trial was carried out to assess how the use of secondgenerationoral contraceptives (treatment A: 150 mg levonorgestrel and 30 mgethinylestradiol) and third-generation oral contraceptives (treatment B: 150 mgdesogestrel and 30 mg ethinylestradiol) varies with respect to their resistance tothe anticoagulant action of activated protein C (APC). Thirty-three healthyfemale volunteers between the ages of 18 and 40 years and without menstrualirregularities were assigned the two oral contraceptive preparations in randomorder (AB or BA).The first oral contraceptive (A or B) was used for two consecutive menstrualcycles (Period 1) and, after a washout of a further two menstrual cycles (muchlonger than the half-life of each preparation), the volunteers were switched to thesecond preparation (B or A) for two cycles (Period 2). Blood samples wereobtained between days 18 and 21 of all six menstrual cycles – one at baselinebefore starting either treatment, two during administration of the firstpreparation, one during the last cycle of the washout period, and two duringadministration of the second preparation. The study concluded that, comparedwith levonorgestrel (A), the desogestrel-containing oral contraceptive treatment(B) conferred significant additional resistance to APC. A summary of the keyfeatures of the two crossover studies is given in Table 1.93