XACIATO: Package Insert and Label Information (Page 2 of 2)

13. NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Long term studies in animals to evaluate carcinogenic potential have not been performed with XACIATO, or the active ingredient, clindamycin phosphate.

Mutagenesis

The genotoxic potential of clindamycin has been evaluated in a rat micronucleus test and an Ames Salmonella reversion test. Both tests were negative.

Impairment of Fertility

Fertility studies in rats treated vaginally with 2 mg/day clindamycin phosphate (0.1g/day XACIATO) or orally with 300 mg/kg/day (doses that are approximately equivalent to or 29-times the MRHD based on BSA comparisons, respectively) revealed no effects on fertility or mating ability.

14. CLINICAL STUDIES

The efficacy of XACIATO as a treatment of bacterial vaginosis (BV) in females 12 years of age and older was demonstrated in a randomized, double-blind, placebo-controlled clinical study (Trial 1, NCT04370548). A single dose of XACIATO (clindamycin phosphate vaginal gel, 2%) was compared to a single dose of placebo vaginal gel (hydroxyethylcellulose [HEC] Universal Placebo Gel) for the treatment of BV. Patients were evaluated at 3 timepoints: a Day 1 screening/randomization visit, a Day 7 to 14 Interim Assessment visit, and a Day 21 to 30 Test of Cure visit. The total study duration was up to approximately 1 month for each individual patient.

To be eligible, patients had to have a clinical diagnosis of BV defined as an off-white (milky or gray), thin, homogeneous discharge with minimal or absent pruritus and inflammation of the vulva and vagina, clue cells > 20% of the total epithelial cells on microscopic examination of the saline wet mount, vaginal secretion pH of > 4.5, and a fishy odor of the vaginal discharge with the addition of a drop of 10% KOH (i.e., a positive whiff test).

The 307 patients were randomized in a 2:1 ratio, with 204 in the XACIATO group and 103 in the placebo group. The modified Intent-To-Treat (mITT) Population excluded women with a positive test result for other concomitant vaginal or cervical infections at baseline, including a positive vaginal culture for Candida spp. or who had a baseline Nugent score of < 7.

Clinical Cure was defined as resolution of the abnormal vaginal discharge associated with BV, a negative 10% KOH whiff test, and clue cells < 20% of the total epithelial cells in the saline wet mount. Bacteriological Cure was defined as a Nugent score < 4. Therapeutic Cure was defined as the presence of both a Clinical Cure and Bacteriological Cure.

In the mITT population, a statistically significantly greater percentage of patients experienced Clinical Cure, Bacteriological Cure, and Therapeutic Cure at the Test of Cure (Day 21-30) visit in the XACIATO arm compared to placebo (Table 2). Statistically significant results for the endpoints were also achieved at the Interim Assessment visit (Day 7-14).

Table 2: Summary of Clinical Cure, Bacteriological Cure, and Therapeutic Cure (Modified Intent-to-Treat Population) in Trial 1

Interim Assessment visit (day 7-14)

Test of Cure visit (day 21-30)

Parameter

XACIATO (N = 122) n (%)

Placebo (N = 59) n (%)

TreatmentDifference (%)[95% ConfidenceInterval]

XACIATO (N = 122) n (%)

Placebo (N = 59) n (%)

Treatment Difference (%)[95% Confidence Interval]

Clinical Cure

93 (76.2)

14 (23.7)

52.5 (38.0, 67.0)

86 (70.5)

21 (35.6)

34.9 (19.0, 50.8)

Bacteriological Cure

50 (41.0)

2 ( 3.4)

37.6 (26.5, 48.7)

53 (43.4)

3 ( 5.1)

38.4 (26.7, 50.1)

Therapeutic Cure

43 (35.2)

0

35.2 (25.5, 45.0)

45 (36.9)

3 ( 5.1)

31.8 (20.3, 43.3)

All P-values for differences between treatment groups were <0.001 (from Cochran-Mantel-Haenszel test with strata of study site and race — African American or all other races).

The percentage of patients with Clinical Cure at the Test of Cure visit was also significantly higher in the XACIATO group compared to the placebo group among the subsets of patients defined by prior episodes of bacterial vaginosis (≤ 3 episodes and >3 episodes in the previous 12 months) at 71.3% (72/101) for XACIATO and 39.1% (18/46) placebo, and 70.0% (14/20) for XACIATO and 23.1% (3/13) placebo, respectively.

16. HOW SUPPLIED/STORAGE AND HANDLING

XACIATO vaginal gel, 2% is a clear, colorless, viscous gel supplied in a carton containing one 25-gram tube of vaginal gel and one vaginal applicator. One single-dose, user-filled disposable applicator delivers 5 g of gel containing 100 mg of clindamycin. NDC number 81505-100-25.

Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room temperature].

17. PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Instructions for Use).

Vaginal Intercourse and Use with Vaginal Products

Instruct the patients not to engage in vaginal intercourse or use other vaginal products (such as tampons or douches) during treatment with XACIATO and for 3 days after using XACIATO.

Use with Polyurethane Condoms

Advise the patient that XACIATO may weaken polyurethane condoms. Therefore, use of polyurethane condoms concurrently or for 7 days following treatment with XACIATO is not recommended. During this time period polyurethane condoms may not be reliable for preventing pregnancy or for protecting against transmission of HIV and other sexually transmitted diseases. Latex or polyisoprene condoms should be used [see Warnings and Precautions (5.2)].

Vaginal Candida Infections

Inform the patient that vaginal yeast infections can occur following use of XACIATO and may require treatment with an antifungal drug [see Warnings and Precautions (5.3), Adverse Reactions (6.1)].

Manufactured for:

Daré Bioscience, Inc.
3655 Nobel Drive, Suite 260San Diego, CA 92122

INSTRUCTIONS FOR USE XACIATO™ [zah-she-AH-toe] (clindamycin phosphate vaginal gel 2%)

For vaginal use only. Do not use in the eyes or mouth, or on your skin.

Read these Instructions for Use before you use XACIATO™ and each time you get a refill as there may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment.

Important Information

  • Use XACIATO exactly as your healthcare provider tells you to use it.
  • Use 1 filled applicator of XACIATO gel in your vagina.
  • Do not use any medicine from the tube or applicator more than 1 time. The XACIATO gel is for 1 time (single-use) only.
  • Do not have vaginal sex or use vaginal products (such as tampons or douches) during treatment with XACIATO gel and for 3 days after using XACIATO gel.
  • Do not use polyurethane condoms during treatment with XACIATO gel and for 7 days after using XACIATO gel. XACIATO gel may weaken polyurethane condoms. Latex or polyisoprene condoms should be used.
  • If you have questions or if your vaginal symptoms do not go away, contact your healthcare provider.

How do I store XACIATO?

  • Store XACIATO gel at room temperature between 68° to 77°F (20° to 25°C).
  • Do not store in the refrigerator or freezer.

Store XACIATO gel and all medicines out of the reach of children.

You will need the following included supplies (see Figure A):

  • 1 single use tube containing the XACIATO gel
  • 1 empty applicator, to fill and deliver the single dose of medicine.
figure-a
Step 1. Remove the applicator and tube from the container box.

Step 2. Open the tube.

  • Unscrew the cap from the tube (see Figure B1).
  • Puncture the seal on the tube using the pointed tip on the cap by pushing the cap straight onto the tube (see Figure B2).
  • Do not use the tube if it looks like it has been opened before.
  • Do not use the tube if the seal is damaged or broken.
figure-b

Step 3. Fill the applicator.

  • While holding the applicator by the grip, screw the tip of the applicator (other end from the grip) onto the tube until it feels secure (see Figure C1).
  • Leave plunger inside the applicator.
  • Squeeze the tube from the bottom to push the XACIATO gel into the applicator (see Figure C2).
  • The XACIATO gel will push the plunger up as the applicator fills (see Figure C3).
  • Continue to fill the applicator until you see the black line on the plunger outside the applicator (see Figure C4).
  • Unscrew the filled applicator from the tube.
figure-c
(click image for full-size original)

Step 4. Prepare to insert the filled applicator.

  • Lie on your back with your knees bent or in any comfortable position (see Figure D).
figure-d
Step 5. Insert the filled applicator.
  • Hold the filled applicator by the grip and gently insert the tip of the applicator into your vagina as far as it will comfortably go (see Figure E).
figure-e
Step 6. Push the plunger.
  • While holding the applicator in place, slowly push the plunger until it stops, to release all the XACIATO gel into your vagina (see Figure F).
figure-f
Step 7. Remove the empty applicator from your vagina.
Step 8. Place the used applicator and tube in the container box and throw away (dispose of) in your household trash.

This Instructions for Use has been approved by the U.S. Food and Drug Administration. 12/2021

Carton

Carton
(click image for full-size original)

Label

label
(click image for full-size original)
XACIATO clindamycin phosphate gel
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:81505-100
Route of Administration VAGINAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
Clindamycin phosphate (CLINDAMYCIN) CLINDAMYCIN 20 mg in 1 g
Inactive Ingredients
Ingredient Name Strength
BENZYL ALCOHOL
CITRIC ACID MONOHYDRATE
POLOXAMER 407
WATER
SODIUM CITRATE
XANTHAN GUM
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:81505-100-25 25 g in 1 TUBE None
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA215650 12/21/2021
Labeler — Daré Bioscience, Inc. (788494669)
Establishment
Name Address ID/FEI Operations
DPT Laboratories, Ltd. 832224526 manufacture (81505-100), analysis (81505-100), pack (81505-100)

Revised: 12/2021 Daré Bioscience, Inc.

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