Evaluation of Telmisartan/Amlodipine and Telmisartan/Amlodipine/Hydrochlorothiazide on 24-Hour Blood Pressure Control in Arterial Hypertension Patients

The primary objective of this study is to evaluate the **efficacy** of treatment with a single-pill combination (SPC) of telmisartan/amlodipine (T/A) and SPC of telmisartan/amlodipine/hydrochlorothiazide (T/A/HCTZ) on 24-hour blood pressure (BP) reduction after 16 weeks of treatment in patients with Grade 1, Grade 2, or Grade 3 arterial hypertension. This is clinically relevant as effective management of blood pressure is crucial in reducing the risk of cardiovascular events and improving patient outcomes in individuals with arterial hypertension.

Secondary objectives include assessing the efficacy of treatment with SPC of T/A and SPC of T/A/HCTZ on office BP control and on 24-hour BP variability after 16 weeks of treatment in patients with Grade 1, Grade 2, or Grade 3 arterial hypertension. These secondary measures provide additional insights into the treatment's impact on blood pressure stability and control, which are important for comprehensive hypertension management.

The clinical trial involves a total of **81 participants** diagnosed with **arterial hypertension**, specifically targeting individuals with Grade 1, Grade 2, or Grade 3 hypertension. The study population includes both male and female subjects aged 18 years and older. Participants were selected based on their diagnosis of hypertension at two separate visits, with an average 24-hour systolic blood pressure (SBP) of at least 130 mmHg and/or diastolic blood pressure (DBP) of at least 80 mmHg, as measured by ambulatory blood pressure monitoring (ABPM). The trial includes individuals who are either treatment-naïve or have uncontrolled hypertension on existing antihypertensive monotherapy or dual combination therapy, excluding those already on telmisartan and amlodipine therapy. Participants are required to have the ability to adhere to the trial protocol and must have voluntarily signed informed consent forms, including consent for the collection and processing of personal data for statistical analysis and reporting. The study does not involve a vulnerable population, and no specific lifestyle considerations such as diet or physical activity are highlighted in the selection criteria.

The clinical trial is designed to evaluate the efficacy of a single-pill combination of **telmisartan**/**amlodipine** and **telmisartan**/**amlodipine**/**hydrochlorothiazide** in reducing 24-hour blood pressure in patients with arterial hypertension. This study is a randomized, double-blind, controlled trial with an estimated duration of 16 weeks. The trial will commence with a screening visit to confirm eligibility based on specific inclusion criteria, such as diagnosed Grade 1, Grade 2, or Grade 3 arterial hypertension and the ability to adhere to the trial protocol. Participants will be required to have an average 24-hour systolic blood pressure (SBP) of at least 130 mmHg or diastolic blood pressure (DBP) of at least 80 mmHg, as measured by ambulatory blood pressure monitoring at baseline.

Following the screening, eligible participants will be randomized to receive either the test medication or a control for the duration of the study. The trial will include several follow-up visits at weeks 4, 8, 12, and 16 to monitor blood pressure changes and assess the primary and secondary endpoints. The primary endpoint is the mean absolute change in 24-hour SBP after 16 weeks of treatment. Secondary endpoints include changes in average real variability of 24-hour SBP and DBP, office SBP and DBP, and pulse wave velocity.

The expected length of participant involvement is approximately 16 weeks, with conditions for early termination including non-compliance with the study protocol or adverse events that may compromise participant safety. The trial is set to conclude with an end-of-study visit to evaluate the overall efficacy and safety of the treatment. The study aims to provide evidence-based data on the effectiveness of the single-pill combination therapy in managing arterial hypertension.

The clinical trial involves the administration of several experimental medications, primarily focusing on the combination of **telmisartan** and **amlodipine**. The first experimental medication is Teldipin, available in two formulations: 80 mg of telmisartan combined with either 5 mg or 10 mg of amlodipine. These medications are provided in tablet form and are administered orally. The maximum daily dose for the 80 mg + 5 mg formulation is 85 mg, with a total dose amount of 5440 mg over the treatment period. For the 80 mg + 10 mg formulation, the maximum daily dose is 90 mg, with a total dose amount of 10080 mg. The treatment period for both formulations is 16 weeks.

Another experimental medication is Telassmo, which also comes in two formulations: 80 mg of telmisartan with either 5 mg or 10 mg of amlodipine, and 40 mg of telmisartan with 5 mg of amlodipine. These are also in tablet form and administered orally. The maximum daily dose for the 80 mg + 5 mg formulation is 85 mg, with a total dose amount of 9520 mg, while the 80 mg + 10 mg formulation has a maximum daily dose of 90 mg and a total dose amount of 10080 mg. The 40 mg + 5 mg formulation has a maximum daily dose of 45 mg and a total dose amount of 5040 mg. The treatment period for all formulations is 16 weeks.

Tamloset is another medication used in the trial, available in three formulations: 80 mg of telmisartan with either 5 mg or 10 mg of amlodipine, and 40 mg of telmisartan with 5 mg of amlodipine. These are administered orally in tablet form. The maximum daily dose for the 80 mg + 5 mg formulation is 85 mg, with a total dose amount of 9520 mg, while the 80 mg + 10 mg formulation has a maximum daily dose of 90 mg and a total dose amount of 10080 mg. The 40 mg + 5 mg formulation has a maximum daily dose of 45 mg and a total dose amount of 5040 mg. The treatment period for all formulations is 16 weeks.

The trial also includes a combination medication containing **telmisartan**, **amlodipine**, and **hydrochlorothiazide**. This medication is available in tablet form and administered orally. The maximum daily dose for this combination is 115 mg, with a total dose amount of 12880 mg over the treatment period of 16 weeks. This combination is also available in formulations with maximum daily doses of 102.5 mg and 97.5 mg, with total dose amounts of 11480 mg and 10920 mg, respectively, over the same treatment period.

All medications are manufactured by KRKA, D.D., Novo Mesto, and are chemically synthesized. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen. The trial aims to assess the efficacy of these single-pill combinations in reducing 24-hour blood pressure, blood pressure variability, and office blood pressure control in patients with arterial hypertension.

The efficacy of the clinical trial will be assessed by evaluating the impact of the single-pill combination (SPC) of telmisartan/amlodipine (T/A) and telmisartan/amlodipine/hydrochlorothiazide (T/A/HCTZ) on 24-hour blood pressure (BP) reduction in patients with Grade 1, Grade 2, or Grade 3 **arterial hypertension**. The primary endpoint is the mean absolute change of 24-hour systolic blood pressure (SBP) after 16 weeks of treatment, measured from baseline to Visit 7. Secondary endpoints include the mean change in average real variability of 24-hour SBP and diastolic blood pressure (DBP), mean absolute change of 24-hour DBP, and mean absolute and relative changes of office SBP and DBP at weeks 4, 8, 12, and 16. Additional secondary endpoints involve the mean absolute change of calculated central SBP and DBP, mean stiffness index (SI), and mean absolute change of pulse wave velocity (PWV) after 16 weeks of treatment.

Measurements will be conducted using ambulatory blood pressure monitoring (ABPM) devices to obtain average 24-hour SBP and DBP at the study baseline. The trial will follow a structured schedule with assessments at baseline and subsequent visits at weeks 4, 8, 12, and 16. Data collection will focus on both office and 24-hour BP readings, ensuring comprehensive evaluation of the treatment's efficacy. The analysis will include comparisons of BP changes across different patient groups, such as dipping, extreme dipping, and non-dipping patients, to provide insights into the treatment's effectiveness across various patient profiles.