Study in post-menopausal women comparing a new cream against EstroGel
Research type
Research Study
Full title
A Phase I, Randomized, Open-Label, Single Center, Cross-over Study to Investigate the Pharmacokinetics and Safety following a Single Application of Three Different Doses 0.5 gm (0.5 mg estradiol), 0.75 gm (0.75 mg estradiol) and 1.25 gm (1.25 mg estradiol), a Transdermal Estradiol Cream (VML-0203), in comparison to a single dose of EstroGelTM 1.25 gm (1 unit/0.75 mg of estradiol) to healthy post-menopausal women.
IRAS ID
230972
Contact name
Annelize Koch
Contact email
Sponsor organisation
Viramal Ltd
Eudract number
2017-002759-27
Duration of Study in the UK
0 years, 2 months, 5 days
Research summary
Summary of Research
This study is made up of four parts, where three different strengths of a test drug (VML-0203) are compared against a marketed drug called EstroGelTM.
The test drug (VML-0203) is a topical cream that’s applied to the upper arm. The cream is proposed help relieve the symptoms associated with being post-menopausal, where there are chronic low levels of oestrogen.
The test drug will be compared against EstroGelTM. Which is an established drug used within the US market.
For this study we will recruit 20 healthy naturally and surgically post-menopausal women.We will assess the way the body handles the drug. In order to do this, we will take blood samples at pre-determined time points.
Summary of Results
The purpose of this study was to investigate the study drug VML-0203.The main objectives of the study were as follows:
- To evaluate and compare the bioavailability (the degree and rate at which a substance (such as a drug) is absorbed into the body or is made available at the site of its’ desired effect) of three different strengths of VML-0203 compared to a marketed product EstroGelTM.
- To determine the safety and tolerability (degree to which side effects of a drug can be tolerated) of estradiol and estrone when it is administered as single doses in two different forms i.e., as three different strengths of VML-0203 and one single dose of a marketed product EstroGelTM.
The study comprised of a screening visit, 4 treatment periods (each 4 days in duration) and a post study follow up visit (5-7 days after the last dose). At each treatment period, participants were administered one of the following study drugs in a randomised fashion:
- Test IMP: a single dose of 0.5 g VML-0203 cream.
- Test IMP: a single dose of 0.75 g VML-0203 cream.
- Test IMP: a single dose of 1.25 g VML-0203 cream.
- Reference IMP: a single dose of 1.25 g EstroGelTM.
Blood samples were taken at each treatment period in order to measure the levels of estradiol and estrone in the blood and to compare how these varied between the various dose strengths of VML-0203 and the reference product EstroGelTM. The below section outlines the key outcomes based on the study data generated.
With respect to the safety objectives of the study, the following outcomes were reported:
- There were no safety concerns following application of VML-0203 and EstroGelTM IMPs in healthy post-menopausal women. There were no clinically significant changes in any of the safety parameters measured i.e., laboratory safety tests, vital signs or ECGs. In addition, there were no visible observed reactions at the site of application of the products and no significant trends or effects observed between 0.5, 0.75 and 1.25 g VML-0203 or between VML-0203 and EstroGelTM.
- All of the reported side effects in the study were considered to be mild to moderate in severity and resolved prior to completion of the study. In addition, the majority of effects were considered to not be related to VML-0203 and EstroGelTM and resolved without treatment (other than administration of paracetamol where required). Further to this, the reported effects did not increase or change in severity as the doses of VML-0203 were increased.
As it relates to the other objectives of the study, the following outcomes were reported:
- Treatment with a single dose of VML-0203 at 1.25 mg increased the levels of estradiol to a threshold beyond the menopausal level from approximately 16 h – 20 h post-dose.
- With respect to the assessment of bioavailability, the levels of estradiol and estrone in the blood improved with increasing dose strengths of VML-0203; however the data is considered to be variable in nature. Further to this the levels of estradiol and estrone across all dose strengths of VML-0203 were overall lower when compared with EstroGelTM.
- There was no observed difference in the time taken for the levels of estradiol and estrone to reach their highest level across any of the dose strengths of VML-0203 and EstroGelTM.
- VML-0203 successfully delivered estradiol when administered to one-side of the arm or whole arm. Overall, the results for application to the whole arm and one side of the arm followed a similar pattern in participants who had lower estradiol and estrone levels observed for VML 0203 when compared to EstroGelTM. When whole arm application of VML-0203 was compared to application to one side of the arm, there was a consistent increase in the levels of estradiol and estrone for VML-0203 following application to the whole arm. However, no formal analysis was conducted.
In summary, the data gathered during the study was considered sufficient to meet the objectives of the study.
REC name
Wales REC 2
REC reference
17/WA/0350
Date of REC Opinion
4 Dec 2017
REC opinion
Further Information Favourable Opinion