Novel low-dose triple single-pill combination shows efficacy and tolerability in two international trials

A low-dose triple single-pill combination was effective at lowering blood pressure (BP) in two trials presented in a Hot Line session today at ESC Congress 2024.

“Globally, most people treated for high BP do not achieve adequate control, primarily due to continued use of low-efficacy regimens including monotherapy. Single-pill combinations of different low-dose drugs hold promise for improving hypertension management by virtue of additive benefits, rapid action and a low risk of adverse events.

“We developed a triple single-pill combination, GMRx2, and tested this in a placebo-controlled trial to assess the product as a whole, and in a trial against three different dual therapies, to assess each component one by one. We are encouraged by the clinically meaningful BP improvements observed,” explained Principal Investigator, Professor Anthony Rodgers of the George Institute for Global Health, University of New South Wales, Australia.

GMRx2 contains telmisartan, amlodipine and indapamide in three dose strengths: triple quarter doses (10 mg, 1.25 mg and 0.625 mg, respectively), triple half doses (20 mg, 2.5 mg and 1.25 mg) or triple standard doses (40 mg, 5 mg and 2.5 mg).

The international placebo-controlled double-blind trial investigated GMRx2 at quarter and half doses. The trial enrolled 295 adults with hypertension receiving 0–1 BP-lowering drugs. After a 2-week placebo run-in period during which any BP-lowering medication was stopped, patients with home systolic BP 130–154 mmHg were eligible for randomization in a 2:2:1 ratio to GMRx2 quarter dose, GMRx2 half dose or placebo. The primary efficacy outcome was the mean change in home systolic BP from baseline to week 4 and the primary safety outcome was treatment withdrawal due to an adverse event.

Mean clinic BP was 138/86 mmHg following the run-in period. At week 4, the placebo-corrected difference in home systolic BP was −7.3 mmHg (95% confidence interval [CI] −4.5 to −10.8) with the GMRx2 quarter dose and −8.2 mmHg (−5.2 to −11.3) with the GMRx2 half dose. Clinic BP control (<140/90 mmHg) was achieved in 37% of participants with placebo, and by 65% and 70% of participants in the GMRx2 quarter- and half-dose groups, respectively (both doses p<0.001 vs. placebo). Withdrawal of treatment due to adverse events occurred in 1.6% of participants in the placebo group and 0% and 5.1% of participants in the GMRx2 quarter- and half-dose groups, respectively.

The active-controlled double-blind trial investigated GMRx2 vs. dual combinations of its components, with participants recruited from Australia, Czech Republic, New Zealand, Poland, Sri Lanka, UK and the U.S.. The trial enrolled 1,385 adults with hypertension receiving 0–3 BP-lowering drugs with screening systolic BP of 140–179 mmHg (on 0 drugs) to 110–150 mmHg (on 3 drugs). In a 4-week active run-in period, existing medications were switched to GMRx2 half dose.

Participants were then randomized in a 2:1:1:1 ratio to continued GMRx2 half dose or each possible dual combination of components at half doses (telmisartan 20 mg/amlodipine 2.5 mg, telmisartan 20 mg/indapamide 1.25 mg or amlodipine 2.5 mg/indapamide 1.25 mg). At week 6, doses were doubled in all groups, unless there was a clinical contraindication. The primary efficacy outcome was mean change in home systolic BP from baseline to week 12.

Mean clinic BP was 142/85 mmHg at screening and 133/81 mmHg after the run-in period. At week 12, home BP was lower with GMRx2 than each of the dual combinations: reductions compared with the telmisartan-indapamide, telmisartan-amlodipine and amlodipine-indapamide groups were 2.5/2.1, 5.4/3.4 and 4.4/3.6 mmHg, respectively (all p<0.0001). The proportion of participants with clinic BP <140/90 mmHg at week 12 was 74% with GMRx2, 61% with telmisartan-indapamide, 61% with telmisartan-amlodipine and 53% with amlodipine-indapamide (with comparisons vs. GMRx2 all p≤0.0001).

Withdrawal of treatment due to adverse events occurred in 2.0% of the GMRx2 participants and 1.4%, 1.1% and 1.4% of telmisartan-indapamide, telmisartan-amlodipine and amlodipine-indapamide groups, respectively.

“GMRx2 reduced BP quickly in mild-to-moderate hypertension and more effectively than dual therapy in a broad, large hypertensive population, without safety concerns. The availability of a single-pill combination could help to reduce current therapeutic inertia, helping patients achieve BP control quickly in a small number of steps, with potential benefits for improved adherence,” concluded Professor Rodgers.