PK Effects of IP2015 in Healthy Males Via Intradermal Capsaicin Model
Research type
Research Study
Full title
A Randomised, Double Blind, Placebo Controlled Study to Investigate the Pharmacodynamic Effects of IP2015 in Healthy Male Subjects Using the Intradermal Capsaicin Model
IRAS ID
303416
Contact name
Ezanul Wahab
Contact email
Sponsor organisation
Initiator Pharma
Eudract number
2021-003628-33
Duration of Study in the UK
0 years, 6 months, 30 days
Research summary
Summary of Research
The purpose of this study is to test a drug called IP2015 that is being developed for the treatment of neuropathic pain. Pain is a complex medical condition with multiple contributing factors. It is the most common reason for physician consultation in most developed countries and can have a strong impact on activities of daily living and quality of life. When the nerves outside of the brain and spinal cord become damaged, a condition called peripheral neuropathy can develop. Neuropathic pain often affects people with diabetes. Currently, 200 million people worldwide suffer from neuropathic pain, also known as diabetic polyneuropathy (DPN).The study drug is a new compound which has shown to be more effective at alleviating neuropathic pain in animal pain models compared to some of the currently available therapeutic interventions.
Capsaicin is an active molecule in hot chilli peppers and is a chemical irritant in humans; it produces a burning sensation when it comes into contact with human skin. The symptoms generated by exposure to Capsaicin are similar to those seen in neuropathic pain; therefore, this pain model may be useful in testing drugs with a potential for treating this condition. Participants will therefore receive capsaicin injections into the skin on the inside of the forearm post dosing during each treatment period to measure response.
It is planned to enrol 24 participants into 6 groups, consisting of 4 participants each. Each participant will have 4 Treatment Periods, in which they will be randomised to receive a single dose of either 5 mg IP2015, 10 mg IP2015, 300 mg pregabalin or placebo in each Treatment Period. Each participant will receive each treatment once only.
The study will be run in a Phase I Unit within the UK, and study participation is expected to last 9 weeks.
Summary of Results
Why Was This Study Conducted?Neuropathic pain is often described as a shooting or burning pain, which can come and go, but is often chronic (long-term). The prevalence of neuropathic pain is between 6.9 to 10%, and it often affects people with diabetes. Currently, 200 million people worldwide suffer from neuropathic pain, also known as diabetic polyneuropathy. Unlike most other types of pain, neuropathic pain does not usually get better with common painkillers, such as paracetamol and ibuprofen, and other medications are often used. However, these medications can have a variety of undesirable side effects. Therefore, there is an unmet need for new treatments for neuropathic pain.
This Phase I study was a double-blind, placebo-controlled study in 24 healthy male participants to test a drug called IP2015 that is being developed for the treatment of neuropathic pain. The effects on pain measures of single doses of IP2015 (a low and a high dose) compared to pregabalin (a standard treatment used to treat neuropathic pain) and placebo were measured in this study. The pain was induced by intradermal capsaicin in a human experimental pain model. The objective of the study in healthy participants was to validate and demonstrate that the effect of IP2015 in preclinical animal models can be translated into pain relief in the human setting.
The pain assessments in the study covered a range of pain measures that were assessed following an intradermal capsaicin injection in the forearm. These pain measures included allodynia (extreme sensitivity to touch), hyperalgesia (an increased sensitivity to feeling pain and an extreme response to pain) and subjective ratings of pain. Quantitative Sensory Testing battery tests were also performed at two sites on the forearm. One site was the most recent capsaicin injection site, and the other was at an equivalent point on the opposite forearm. The QST battery includes 12 different ways of assessing pain signals (warm, cold and pressure tests on the skin of the participants).
Who Took Part in the Study?
Twenty-five healthy male participants were divided into 4 groups by chance (randomised) to reduce differences between the groups. Twenty-four subjects completed the study; one participant left the study before the study completed. Each participant took part in 4 Treatment Periods; in each Treatment Period, participants were orally administered a combination of two treatments. Participants were administered a different treatment combination in each Treatment Period, and they received each treatment combination once. The treatment combinations were:
• A low dose of IP2015 and placebo
• A high dose of IP2015 and placebo
• Placebo and Pregabalin
• Two doses of placebo
Overall, all participants in the study were exposed to a single dose of the low dose of IP2015, the high dose of IP2015 and pregabalin.What Were the Overall Results of the Study?
Side effects include unwanted medical issues that happen during the study, even if they may not be related to IP2015. Not all participants in this study experienced side effects and no serious side effects were reported. Side effects that were considered to be related to the treatment were reported following administration of all four three active treatments in this study – and also in the placebo treated group. The highest level and intensity of adverse eventsside effects were observed in the pregabalin treatment group (predominantly dizziness, as expected). The IP2015 treatment groups had less and milder observations (some with headache and nausea, respectively).
All other side effects were reported inless by less than 10% of participants in the study. No safety concerns could be attributed to treatment with IP2015 in this study.IP2015 demonstrated a statistically significant effect on allodynia and showed a dose dependent effect on the other measured pain parameters. Pregabalin and IP2015 tended to reduce hyperalgesia, although the effects on hyperalgesia were not statistically significant compared to participants who were administered placebo.
In the assessment of subjective pain ratings, the average values for IP2015 showed 2- and 5 fold higher effects compared to pregabalin and placebo, respectively. In support of these positive results, IP2015 demonstrated data in the Quantitative Sensory Test pain assessments related to pain in line with the primary pain assessments provided above. In the heat detection and thermal sensory (warm) threshold tests, respectively, statistically significant outcomes were detected for IP2015 when tested in participants administered IP2015.
How Has This Study Helped Patients and Researchers?
This study was conducted in healthy male participants aged 18 to 55 years. The results from this study are limited to the particular people studied and cannot be assumed to be true for everybody. Not all participants in each part of the study had the same results.
This research helps future patients and families by helping us understand more about each medicine being studied. Findings from this study will be used in other studies to compare this drug with other treatments for neuropathic pain.
Where Can I Find More Information About This Study?
To learn more about this study, visit https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DouFFm-2FZqrUn2jjUD5TieZBfigX0bV4wUGi1E343XhAsgWUztRtRZxRO8OoB8GKXTHgdA_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YLkWTKMZ-2BZQaBEJs-2F6hexdHaMZmI4-2Bp5UjWMjbi-2B6mzRHCBryktL2vvQCAtxUSSjTEV-2FZBTLcTII3AOC-2FOakgHby8cojiN4eW6nf3cefnWFPwiCfrtyD-2BoHwK7uCLVuIpojK8fQfc-2Fvi-2BFmYYwsfzgeV1EiKBF6E5jiyb15JubtZw-3D-3D&data=05%7C01%7Capprovals%40hra.nhs.uk%7C9903ec6e664b4baf38ed08db08ef7571%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638113596781259501%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=%2BkWFdDgrZyym56bWnOlkrps17FAcUv7hZJK81yweQWo%3D&reserved=0
This summary was completed on 25 January 2023. Newer information since this summary was written may now exist. This summary includes only results from one single study. Other studies may find different results.REC name
Wales REC 1
REC reference
21/WA/0308
Date of REC Opinion
13 Sep 2021
REC opinion
Favourable Opinion