A Phase IIb/III Clinical Study to Evaluate the Efficacy and Safety of APC101 in Patients With Postherpetic Neuralgia.

APC101 is a film-forming, sustained-release, and metered-dose topical spray. This investigational product (IP) is formulated with 5% by weight of lidocaine and several excipients. APC101 offers several unique properties or advantages over the first line topical treatment of lidocaine patches, including:

• Can be applied to the area above the neck (face and head).
• Contact-free: eliminating pain when apply to the skin of PHN patients.
• Suitable to apply to uneven skin of PHN patient.
• Less adverse reactions such as skin rash and redness at the application sites.
• Less systemic absorption compared with patch, which shows safer profile.
• Can be administered twice daily as needed.
• The only prescription spray product providing pain relief for PHN with clinical evidence.

This is a Phase IIb/III, randomized, double-blind, placebo-controlled clinical study to evaluate the efficacy and safety of APC101 in patients with PHN.

Participants will be eligible for enrollment in the study only if they meet ALL the following inclusion criteria at the time of screening:

Inclusion criteria

• Males or females ≥ 18 years.
• Female of non-childbearing potential (i.e., 12 months or more of spontaneous amenorrhea without an alternative medical cause, bilateral oophorectomy at least 6 months prior to randomization, hysterectomy with bilateral oophorectomy at least 6 months prior to randomization,.
• Women of childbearing potential (WOCBP) must be confirmed to be not pregnant at Screening Visit.
• Males with sexual partners and females of childbearing potential must agree to use a highly effective contraceptive method:

• Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:

• Oral
• Intravaginal
• Transdermal
• Progestogen-only hormonal contraception associated with inhibition of ovulation:

• Oral
• Injectable
• Implantable
• Intrauterine device (IUD)
• Intrauterine hormone-releasing system (IUS)
• Bilateral tubal occlusion
• Vasectomised partner. Vasectomised partner is a highly effective birth control method provided that partner is the sole sexual partner of the WOCBP study participant and that the vasectomised partner has received medical assessment of the surgical success.
• Sexual abstinence: abstinence is acceptable as a highly effective method of contraception only when it is consistent with the participant's usual and preferred lifestyle. Periodic or situational abstinence will not be considered acceptable for the purposes of meeting contraceptive requirements.

Male participants should use a condom throughout the study. For a non-pregnant WOCBP partner, the highly effective contraception recommendations listed above should also be considered.

Note: Birth control methods considered unacceptable in clinical trials Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea method (LAM) are not acceptable methods of contraception. Female condom and male condom should not be used together.

• Persistent pain for lasting > 3 months from the appearance of herpes zoster rash that is not located in proximity to mucous membranes.
• Diagnosis of PHN based on medical history as judged by investigator.
• Persistent neuropathic pain that involves at least one dermatome and covers ≤420 cm2.
• If the participant has been on stable dose(s) of oral analgesic medication(s) for at least 30 days prior to the Screening Visit, they need to be willing to maintain the respective dose(s) and medication throughout the study.
• Pain intensity score (NRS-11 score) in the target area of ≥ 5 at Screening Visit (Visit 1), and meeting all of the following conditions at Visit 2 (Day 1), prior to randomization:

• Baseline WAPS ≥5, as assessed using NRS-11 score in the target area. Participants with baseline WAPS <5 will be considered screen failures.
• Participants who report an NRS-11 score <5 on ≤ 1 occasion. Participants who report an NRS-11 score <5 on ≥ 2 occasions within a week will be considered screen failures.
• Participants with evaluable WAPS, i.e., with WAPS records of ≥4 out of 7 data points collected during the Run-in period.

Participants with WAPS records of <4 out of 7 data points during the Run-in period will be considered screen failures.

• Skin is intact over the painful area to be treated.
• Able and willing to provide informed consent and comply with study procedures.
• In the opinion of the investigator, the PHN-affected area to be administered study drug will allow adequate contact of the study drug with the skin without affecting any mucous membranes.

Participants meeting ANY of the following exclusion criteria at the time of Screening will not be able to participate in this study.

Exclusion criteria

• Participant has systemic disease that would put him/her at an additional risk or limit his/her ability to participate in the study as judged by the investigator.
• Participant has a history of human immunodeficiency virus, hepatitis C, or hepatitis B.
• Participant has a history of malignancy other than basal cell carcinoma and carcinoma in situ within the past 2 years.
• Participant has a history of mental illness or psychiatric illness, such as dementia, depression, or schizophrenia, that can limit his/her ability to comply with study procedures as judged by the investigator.
• Participant is unable to apply, or to have a caregiver apply, the study spray to the most painful skin segments twice a day as directed.
• Participant has known sensitivity to lidocaine-containing products.
• Participant has active herpes zoster lesions or dermatitis.
• Participant has other condition(s) that cause severe or chronic pain that may impair the self-assessment of the pain due to PHN as judged by the investigator.
• Participant has been treated in the area of PHN with a local anesthetic within 14 days prior to Run-in period or has had a nerve block within 30 days prior to Run-in period.
• Participant is receiving or plans to receive any prohibited medication or therapy for the duration of the study, or is unable to washout these medications or therapies prior to Run-in period.
• Participant has used capsaicin patches within 90 days prior to Run-in period or has used other capsaicin preparations daily in the 90 days prior to Run-in period.
• Pregnant or lactating females.
• Participant has an active history of alcohol or drug abuse.
• Participant has participated in any other investigational study within 30 days prior to Screening Visit.
• Participant or participant's direct family is employed by the sponsor or study staff.
• Participant has any condition that would make him/her unsuitable for the study in the opinion of the investigator or sponsor.