dm+d

23712611000001104

Articles

Safety in Lactation: Drugs for hypertension

23 September 2020Additional information relating to breastfeeding To be used in conjunction with individual drug entries for specific information and guidance. Many of the drugs covered by…
Search Articles

Medicine Compliance Aid Stability

OpsumitActelion Pharmaceuticals UK Ltd

Actelion Pharmaceuticals UK Ltd
Opsumit
Tablets 10mg
A1 · Amber 1Stability data is available in an alternative container (not CAs) that may be extrapolated to support storage in CAs.
Airtight container
Protect from moisture
Store in airtight containers. Protect from moisture
9 November 2015

Lactation Safety Information

No
Sildenafil
No published evidence of safety
Serious adverse effects reported in adults
16 January 2017

New Medicines

OpsumitPulmonary hypertension - management post Fontan procedure in adults and adolescents

Information

Opsumit
Licence extension / variation
Janssen-Cilag
Actelion

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials

Category

Endothelin receptor antagonist. Given in a dose of 10mg daily.
The Fontan operation is a palliative surgical procedure performed in patients with a functional or anatomic single ventricle (also known as univentricular heart) [1]. A 2014 study suggests the UK single ventricle population to be 1040 adults and 1700 children, with an expected increase in adult numbers by 60% in the next decade [2].
Pulmonary hypertension - management post Fontan procedure in adults and adolescents
Oral

OpsumitChronic thromboembolic pulmonary hypertension, inoperable or persistent/recurrent

Information

Opsumit
Licence extension / variation
Janssen-Cilag
Actelion

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Not approved
Yes
Jan 20Actelion plans to collect more data [8].
Nov 19EU MAA withdrawn by the company: at the time of withdrawal, the EMA had concerns that the information provided was insufficient to support the application. It considered that the results of the main study were difficult to interpret, and there were several deviations from the study protocol which may have made the results less reliable [7].
Jan 19FDA issues a complete response letter, not approving Opsumit [6].
Aug 18Filed in EU [5].
May 18Has orphan drug status in US for pulmonary hypertension [4].
Apr 18Actelion files a supplemental NDA (sNDA) to the US FDA for treatment of adults with inoperable CTEPH to improve exercise capacity and pulmonary vascular resistance (PVR). The filing is based on the data from the PII MERIT-1 trial [4].

Category

Endothelin receptor antagonist. Given in a dose of 75mg daily, after initial titration.
Between 0.5% and 4% of patients develop chronic thromboembolic PH (CTEPH) after acute pulmonary embolism. There is an increased risk for patients presenting with large, recurrent or unprovoked clots [1]. In the general population, the incidence of CTEPH is estimated to be approximately 5 cases per million people per year [2].
Chronic thromboembolic pulmonary hypertension, inoperable or persistent/recurrent
Oral

Trial or other data

Mar 22PIII MACiTEPH study to evaluate the effect of macitentan 75 mg versus placebo on exercise capacity at Week 28 in participants with CTEPH is recruiting (NCT04271475). It started in Jul 20. 144 adults will be recruited, including in the US and Europe (incl. UK). In the experimental arm, participants will receive macitentan at a dose of 10mg once daily (OD) for 4 weeks, followed by a dose of macitentan 37.5mg for another 4 weeks and continue with the target dose of macitentan 75mg. Participants who have reached the target dose of 75mg, completed the Double-blind (DB) period up to Week 28 (either on treatment or in Post-treatment observation period [PTOP]) at minimum, may be eligible for transitioning into the Open label (OL) extension period once all participants have completed the DB part of the study, or earlier if they experienced a Clinical event committee (CEC) confirmed clinical worsening event. In the placebo group, participants will receive placebo tablets matching the macitentan 10mg, 37.5mg and 75mg tablets, respectively. Participants who completed the DB period as per protocol either on treatment or in PTOP are eligible for transitioning to the OL extension period and will receive macitentan 75mg after an 8-week double-dummy uptitration (macitentan 10mg for 4 weeks, followed by 37.5mg for another 4 weeks). Primary outcome is change from baseline to week 28 in 6MWD as measured by 6-minute walk test [6MWT] at 28 weeks; collection of these data is due to complete May 24 [9].
Mar 22PII MERIT-2 is due to complete collection of primary outcome data this month. It has recruited 76 patients [9].
Mar 18PII MERIT-2 has completed recruitment ans expects to complete collection of primary outcome data in Dec 20 [3].
Sep 16PII MERIT-1 trial completes. The trial met its primary endpoint indicating a significant reduction in pulmonary vascular resistance (PVR) with macitentan compared with placebo, at week 16 [4].
Feb 15PII extension study to assess the long-term safety, tolerability and efficacy of macitentan in approximately 78 patients starts (MERIT-2; NCT02060721) [3].
Aug 14PII MERIT-1 trial assessing safety, tolerability and efficacy of macitentan 10mg oral tablet, administered once-daily, in patients with inoperable CTEPH starts (AC-055E201; NCT02021292). 78 patients will be enrolled in countries including the US, & EU (plus UK) [3].