Olmesartan medoxomil with hydrochlorothiazide, tablet, 20 mg-12.5 mg, 40 g 12.5 mg, 40 mg-25 mg, Olmetec Plus®, March 2007
Public summary document for Olmesartan medoxomil with hydrochlorothiazide, tablet, 20 mg-12.5 mg, 40 g 12.5 mg, 40 mg-25 mg, Olmetec Plus®, March 2007
Page last updated: 29 June 2007
Public Summary Document
Product: Olmesartan medoxomil with
hydrochlorothiazide, tablet, 20 mg-12.5 mg, 40 g 12.5 mg, 40 mg-25
mg, Olmetec Plus®
Sponsor: Schering-Plough Pty Limited
Date of PBAC Consideration: March 2007
1. Purpose of Application:
The submission sought a restricted listing for the treatment of
hypertension in patients who are not adequately controlled with
either hydrochlorothiazide or olmesartan monotherapy.
The combination product had not previously been considered by the
Olmesartan tablet 10 mg, 20 mg and 40 mg were considered at the November 2005 PBAC meeting following a request from Pfizer Australia Pty Ltd. The PBAC recommended listing on a cost minimisation basis compared to irbesartan with 1 mg olmesartan being equivalent to 7.5 mg irbesartan.
3. Registration Status:
Olmetec Plus was registered by the TGA in June 2006 for: Treatment
of hypertension. Treatment should not be initiated with this fixed
4. Listing requested and PBAC’s view
Hypertension in patients who are not adequately controlled with either hydrochlorothiazide or olmesartan monotherapy
See Recommendation and Reasons for PBAC’s View.
5. Clinical place for the proposed therapy
Olmesartan medoxomil with hydrochlorothiazide will provide another
combination of angiotensin II receptor antagonist (ATRA) and
diuretic for patients with hypertension unresponsive to monotherapy
with either ingredient.
The submission nominated olmesartan medoxomil (olmesartan) and
hydrochlorothiazide (HCTZ) taken concomitantly as the appropriate
7. Clinical trials
The scientific basis of comparison consisted of two randomised controlled trials which involved:
- comparing olmesartan (20 mg) and hydrochlorothiazide (12.5 mg or 25 mg) with olmesartan (20 mg) monotherapy, in patients with diastolic blood pressure (DBP) between 100 and 115mm Hg, over 12 weeks.
- comparing, in a 12 arm randomisation, olmesartan and hydrochlorothiazide (6 dosage combinations) with olmesartan (10 mg, 20 mg or 40 mg) or hydrochlorothiazide (12.5 mg or 25 mg) monotherapy and placebo, in patients with diastolic BP between 100 and 115mm Hg, over 8 weeks.
The full list of trials forming the basis of the submission is tabulated below
Citations of the relevant randomised trials in the submission
|Sellin et al (2005)||Adding hydrochlorothiazide to olmesartan dose dependently improves 24-h blood pressure and response rates in mild-to-moderate hypertension. Journal of Hypertension 23:2083-2092|
|Chrysant et al (2004)||Evaluation of antihypertensive therapy with the combination of olmesartan medoxomil and hydrochlorothiazide. American Journal of Hypertension 17:252|
8. Results of trials
The results of the key trials are summarised in the table
Results of the key trials' primary outcomes: comparison of mean changes in blood pressure between differing dosage combinations
|Olmesartan (mg) / HCTZ (mg)||N||Mean difference (95% CI)||p-value|
|Sellin et al (2005)||Mean change in daytime ambulatory DBP (SD)|
|20 mg / placebo||174||– 2.8 (± 8.4)||-2.20 (-3.93,-0.47)||<0.0001|
|20 mg / 12.5 mg||184||– 5.0 (± 8.3)|
|Chrysant et al (2004)||Mean change in trough seated DBP (SD)|
|20 mg / placebo||41||–13.8 (± 7.4)||-2.60 (-6.67,1.47)||0.21|
|20 mg / 12.5 mg||44||–16.4 (± 11.2)|
|40 mg / placebo||45||–14.6 (± 7.7)||–2.70 (–5.69, 0.29)||0.08|
|40 mg / 12.5 mg||42||–17.3 (± 6.4)|
|40 mg / 12.5 mg||42||–17.3 (± 6.4)||–4.60 (–7.65, –1.55)||0.003|
|40 mg / 25 mg||39||–21.9 (± 7.6)|
DPB = diastolic blood pressure
The secondary outcomes, such as the proportions of participants
whose blood pressure dropped after treatment to a defined norm, did
not show any statistically significant outcomes.
The PBAC noted the sponsor’s Pre-PBAC response observed that although not all analyses were statistically significant, this may be explained by the small number of patients in the Chrysant et al Study.
There were no significant differences reported in the treatment groups and the placebo group with respect to adverse events. In Chrysant et al the overall discontinuation rate due to adverse events of patients who received one or both of the active study drugs was 2.0%. The PBAC noted that the toxicity data in the submission was not well documented.
9. Clinical Claim
he submission described all three fixed dose combination of
olmesartan and hydrochlorothiazide as having significant advantages
in effectiveness over olmesartan or hydrochlorothiazide
See recommendations and Reasons for PBAC’s view
10. Economic analysis
A preliminary economic evaluation was presented. The PBAC agreed
that a cost-minimisation approach was valid.
A modelled economic evaluation was not presented.
11. Estimated PBS Usage and Financial Implications
The likely number of patients treated per year was estimated to be
between 75,000-105,000 patients in Year 4.
The financial cost to the PBS was expected to be cost neutral, for although the predicted numbers of patients to be treated was deemed to be poorly justified by the ESC, each is individually expected to be cost neutral.
12. Recommendation and Reasons
The PBAC recommended listing on a cost-minimisation basis compared
with the corresponding strengths of the hydrochlorothiazide and
olmesartan medoxomil components given concomitantly. The Committee
noted that the olmesartan monotherapy product, recommended for
listing at the November 2005 meeting, will also be listed. This
ensures that the combination product meets the PBAC guidelines for
fixed combination products.
The PBAC recommended the 20 day safety net rule should apply.
OLMESARTAN with HYDROCHLOROTHIAZIDE tablet, 20 mg-12.5 mg, 40 mg-12.5 mg, 40 mg-25 mg
Restriction: Restricted benefit
Hypertension in a patient not adequately controlled with either hydrochlorothiazide or olmesartan medoxomil monotherapy.
Maximum quantity: 30
13. Context for Decision
The PBAC helps decide whether and, if so, how medicines should be
subsidised in Australia. It considers submissions in this context.
A PBAC decision not to recommend listing or not to recommend
changing a listing does not represent a final PBAC view about the
merits of the medicine. A company can resubmit to the PBAC or seek
independent review of the PBAC decision.
14. Sponsor’s Comment
Sponsor chose not to make a comment.