The primary objective of this study was to assess the anti-hypertensive effect of OM/HCTZ 40/12.5 mg combination therapy compared to OM 40 mg monotherapy in lowering sitting diastolic BP in hypertensive patients after 8 weeks of double-blind treatment.

The study consisted of two sequential phases of 8 weeks duration each:

During the first phase, OM 40 mg monotherapy was compared with OM/HCTZ 40/12.5 mg in order to evaluate the additional benefit of OM/HCTZ 40/12.5 mg in the treatment of essential moderate to severe hypertension.

During the second phase, patients whose BP proved to be insufficiently controlled by the OM 40 mg monotherapy were to start OM/HCTZ 40/12.5 mg combination therapy while patients whose BP proved to be insufficiently controlled by the OM/HCTZ 40/12.5 mg combination were to be up-titrated to the OM/HCTZ 40/25 mg combination to evaluate the additional benefit of the up-titrated combination.

The study was be conducted by qualified and experienced personnel with adherence to GCP, current guidelines on the design of studies in hypertension, the applicable regulatory requirements and the ethical principles based on the Declaration of Helsinki.

Methodology:

After the signature of the informed consent, patients were screened for eligibility and eligible patients entered into a pre-randomisation period consisting of a taper-off phase of approximately 1-2 weeks (during which patients treated for hypertension were to discontinue their antihypertensive therapy) followed by a 2-week single-blind placebo run-in phase (Visit 1). After conclusion of the placebo run-in phase (Visit 2), eligible patients were randomised to the double-blind active treatment period which consisted of two phases:

First double-blind treatment phase (Phase A, from Randomisation to Week 8):

Eligible patients with mean sitting sBP ≥ 160 and ≤ 200 mmHg and dBP ≥ 100 mmHg and ≤ 120 mmHg were randomised in a 1:2 ratio to receive either OM 40 mg or OM/HCTZ 40/12.5 mg for a total of 8 weeks of treatment (Phase A). Study visits were held after 4 and 8 weeks of double-blind active treatment (Visit 3 and 4, respectively). After 8 weeks (Visit 4), patients reaching the BP goal of < 140/90 mmHg or < 130/80 mmHg for diabetics were considered as responders. All patients (responders and non-responders) then entered into the titration phase of the study (Phase B):

Second double-blind treatment phase/titration phase (Phase B, from Week 8 to Week 16):

Treatment assignment in the second part of the study was based on the following criteria:

• Responders to Phase A treatment continued to receive the same double-blind treatment for an additional 8 weeks.

• Non-responders Phase A treatment had their treatment assigned as follows:

  • Non-responders to OM 40 mg were treated with OM/HCTZ 40/12.5 mg for an additional 8 weeks.
  • Non-responders to OM/HCTZ 40/12.5 mg were uptitrated to OM/HCTZ 40/25 mg for an additional 8 weeks. During Phase B of the study, visits were held 12 and 16 weeks after randomisation (Visits 5 and 6, respectively).

The study ended at Visit 6 and a final examination was performed. A safety follow-up (SFU) telephone contact was performed 2 weeks after the end of the treatment. An SFU visit was performed if deemed necessary by the investigator.

Sphygmomanometer was used for BP measurement throughout the trial. BP was measured at all visits as nearly as possible at the same time of the day as trough readings (24 ± 2 h after last drug intake) after a 10 minute rest period. Three separate sitting BP measurements were taken at least 1 minute apart from each other. The 3 results were then averaged and rounded to a whole integer.

Patients with sBP values > 200 mmHg and/or dBP values > 120 mmHg at any time during the study were to be discontinued from the study.

Inclusion Criteria:

• Patients with a diagnosis of essential hypertension, either treatment-naive or including currently on anti-hypertensive medication (in Italy only treatment naive patients) in whom it is medically justifiable to withdraw treatment , and who are likely to meet the required BP inclusion criteria at randomisation:

  • Mean sitting dBP ≥ 100 mmHg and ≤ 120 mmHg.
  • Mean sitting sBP ≥ 160 mmHg and ≤ 200 mmHg.

Main Exclusion Criteria:

• Mean sitting sBP values > 200 mmHg and/or dBP > 120 mmHg.
• Pregnant or nursing women.
• Patients with serious disorders which may limit the ability to evaluate the efficacy or safety of the tested medication, including cerebrovascular, cardiovascular, renal, respiratory, hepatic, gastrointestinal, endocrine or metabolic, haematological, oncological, neurological, and psychiatric diseases. The same applies for immunocompromised and/or neutropenic patients.
• Patients with secondary hypertension of any aetiology such as renal disease, pheochromocytoma, or Cushing's syndrome.