Dalvance Drug Information
Generic name: DALBAVANCIN
Uses of Dalvance
Acute Bacterial Skin and Skin Structure Infections
DALVANCE ® is indicated for the treatment of adult and pediatric patients with acute bacterial skin and skin structure infections (ABSSSI) caused by designated susceptible strains of the following Gram-positive microorganisms: Staphylococcus aureus (including methicillin-susceptible and methicillin-resistant isolates), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus dysgalactiae, Streptococcus anginosus group (including S. anginosus, S. intermedius, S. constellatus ) and Enterococcus faecalis (vancomycin susceptible isolates).
Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness
of DALVANCE and other antibacterial agents, DALVANCE should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
Dosage & Administration of Dalvance
| 30 mL/min and above or on regular hemodialysis | 1,500 mg |
|---|---|
| Less than 30 mL/min and not on regular hemodialysis | 1,125 mg |
Side Effects of Dalvance
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of DALVANCE cannot be directly compared to rates in the clinical trials of another drug and may not reflect rates observed in practice. Clinical Trials Experience in Adult Patients Adverse reactions were evaluated for 2,473 patients treated with DALVANCE: 1,778 patients were treated with DALVANCE in seven Phase 2/3 trials comparing DALVANCE to comparator antibacterial drugs and 695 patients were treated with DALVANCE in one Phase 3 trial comparing DALVANCE single and two-dose regimens. The median age of patients treated with DALVANCE was 48 years, ranging between 16 and 93 years.
Patients treated with DALVANCE were predominantly male (59.5%) and White (81.2%). Serious Adverse Reactions and Adverse Reactions Leading to Discontinuation Serious adverse reactions occurred in 121/2,473 (4.9%) of patients treated with any regimen of DALVANCE. In the Phase 2/3 trials comparing DALVANCE to comparator, serious adverse reactions occurred in 109/1,778 (6.1%) of patients in the DALVANCE group and 80/1,224 (6.5%) of patients in the comparator group. In a Phase 3 trial comparing DALVANCE single and two-dose regimens, serious adverse reactions occurred in 7/349 (2.0%) of patients in the DALVANCE single dose group and 5/346 (1.4%) of patients in the DALVANCE two-dose group. DALVANCE was discontinued due to an adverse reaction in 64/2,473 (2.6%) patients treated with any regimen of DALVANCE. In the Phase 2/3 trials comparing DALVANCE to comparator, DALVANCE was discontinued due to an adverse reaction in 53/1,778 (3.0%) of patients in the DALVANCE group and 35/1,224 (2.9%) of patients in the comparator group.
In a Phase 3 trial comparing DALVANCE single and two-dose regimens, DALVANCE was discontinued due to an adverse reaction in 6/349 (1.7%) of patients in the DALVANCE single dose group and 5/346 (1.4%) of patients in the DALVANCE two-dose group. Most Common Adverse Reactions The most common adverse reactions in patients treated with DALVANCE in Phase 2/3 trials were nausea (5.5%), headache (4.7%), and diarrhea (4.4%). The median duration of adverse reactions was 3.0 days in patients treated with DALVANCE. In the Phase 2/3 trials comparing DALVANCE to comparator, the median duration of adverse reactions was 3.0 days for patients in the DALVANCE group and 4.0 days in patients in the comparator group. In a Phase 3 trial comparing DALVANCE single and two-dose regimens, the median duration of adverse reactions was 3.0 days for patients in the DALVANCE single and two-dose group.
Table 2 lists selected adverse reactions occurring in 2% or more of patients treated with DALVANCE in Phase 2/3 clinical trials. Table 2. Selected Adverse Reactions Occurring in ≥ 2% of Patients Receiving DALVANCE in Phase 2/3 Trials (Number (%) of Patients) Adverse Reactions DALVANCE Comparator* (N = 1, 778) (N = 1, 224) Nausea 98 78 Diarrhea 79 72 Headache 83 59 Vomiting 50 37 Rash 48 30 Pruritus 38 41 * Comparators included linezolid, cefazolin, cephalexin, and vancomycin. In the Phase 3 trial comparing the single and two-dose regimen of DALVANCE, the adverse reaction that occurred in 2% or more of patients treated with DALVANCE was nausea (3.4% in the DALVANCE single dose group and 2% in the DALVANCE two-dose group). The following selected adverse reactions were reported in DALVANCE treated patients at a rate of less than 2% in these clinical trials: Blood and lymphatic system disorders : anemia, hemorrhagic anemia, leucopenia, neutropenia, thrombocytopenia, petechiae, eosinophilia, thrombocytosis Gastrointestinal d isorders : gastrointestinal hemorrhage, melena, hematochezia, abdominal pain General d isorders and administration site conditions : infusion-related reactions Hepatobiliary disorders : hepatotoxicity Immune system disorders : anaphylactic reaction Infections and infestations : Clostridioides difficile colitis, oral candidiasis, vulvovaginal mycotic infection Investigations : hepatic transaminases increased, blood alkaline phosphatase increased, international normalized ratio increased, blood lactate dehydrogenase increased, gamma-glutamyl transferase increased Metaboli sm and nutrition disorders : hypoglycemia Nervous s ystem disorders : dizziness Respiratory, thoracic and media s tinal disorders : bronchospasm Skin and s ubcutaneous t issue d isorders : rash, pruritus, urticaria Vascular disorders : flushing, phlebitis, wound hemorrhage, spontaneous hematoma Alanine Aminotransferase (ALT) Elevations Among patients with normal baseline ALT levels treated with DALVANCE 17 (0.8%) had post baseline ALT elevations greater than 3 times the upper limit of normal (ULN) including five subjects with post-baseline ALT values greater than 10 times ULN. Among patients with normal baseline ALT levels treated with non-DALVANCE comparators 2 (0.2%) had post-baseline ALT elevations greater than 3 times the upper limit of normal.
Fifteen of the 17 patients treated with DALVANCE and one comparator patient had underlying conditions which could affect liver enzymes, including chronic viral hepatitis, history of alcohol abuse and metabolic syndrome. In addition, one DALVANCE-treated subject in a Phase 1 trial had post-baseline ALT elevations greater than 20 times ULN. ALT elevations were reversible in all subjects with follow-up assessments. No comparator-treated subject with normal baseline transaminases had post-baseline ALT elevation greater than 10 times ULN. Clinical Trials Experience in Pediatric Patients Adverse reactions were evaluated in one Phase 3 pediatric clinical trial which included 161 pediatric patients from birth to less than 18 years of age with ABSSSI treated with DALVANCE (83 patients treated with a single dose of DALVANCE and 78 patients treated with a two-dose regimen of DALVANCE) and 30 patients treated with comparator agents for a treatment period up to 14 days.
The median age of pediatric patients treated with DALVANCE was 9 years, ranging from birth to <18 years. The majority of patients were male (62.3%) and White (89.0%). The safety findings of DALVANCE in pediatric patients were similar to those observed in adults. Serious Adverse Reactions and Adverse Reactions Leading to Discontinuation Serious adverse reactions (SARs) occurred in 3/161 (1.9%) of patients treated with DALVANCE, all in the single-dose arm.
There were no adverse reactions leading to DALVANCE discontinuation. Most Common Adverse Reactions Most common adverse reaction occurring in more than 1% of pediatric patients 2/161 (1.2%) was pyrexia. Other Adverse Reactions The following selected adverse reactions were reported in DALVANCE-treated patients at a rate of less than 1% in this pediatric clinical trial: Gastrointestinal disorders : diarrhea Nervous system disorders : dizziness Skin and subcutaneous tissue disorders : pruritus
Post Marketing Experience
The following adverse reaction has been identified during post-approval use of dalbavancin. Because the reaction is reported voluntarily from a population of uncertain size, it is not possible to reliably estimate the frequency or establish a causal relationship to drug exposure. General disorders and administration site conditions: Back pain as an infusion-related reaction.
Warnings & Cautions for Dalvance
Hypersensitivity Reactions Serious hypersensitivity (anaphylactic) and skin reactions have been reported in
patients treated with DALVANCE. If an allergic reaction to DALVANCE occurs, discontinue treatment with DALVANCE and institute appropriate therapy for the allergic reaction. Before using DALVANCE, inquire carefully about previous hypersensitivity reactions to other glycopeptides. Due to the possibility of cross-sensitivity, carefully monitor for signs of hypersensitivity during treatment with DALVANCE in patients with a history of glycopeptide allergy .
Infusion - Related Reactions
DALVANCE is administered via intravenous infusion, using a total infusion time of 30 minutes to minimize the risk of infusion-related reactions. Rapid intravenous infusions of DALVANCE can cause flushing of the upper body, urticaria, pruritus, rash, and/or back pain. Stopping or slowing the infusion may result in cessation of these reactions.
Hepatic Effects
In Phase 2 and 3 clinical trials, more DALVANCE than comparator-treated subjects with normal baseline transaminase levels had post-baseline alanine aminotransferase (ALT) elevation greater than 3 times the upper limit of normal (ULN). Overall, abnormalities in liver tests (ALT, AST, bilirubin) were reported with similar frequency in the DALVANCE and comparator arms.
Clostridioides difficile - Associated Diarrhea Clostridioides difficile -associated diarrhea (CDAD) has been
reported in users of nearly all systemic antibacterial drugs, including DALVANCE, with severity ranging from mild diarrhea to fatal colitis. Treatment with antibacterial agents can alter the normal flora of the colon, and may permit overgrowth of C. difficile. C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin-producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antibacterial therapy and may require colectomy.
CDAD must be considered in all patients who present with diarrhea following antibacterial use. Careful medical history is necessary because CDAD has been reported to occur more than 2 months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibacterial use not directed against C. difficile should be discontinued, if possible.
Appropriate measures such as fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
Development of Drug-Resistant Bacteria Prescribing
DALVANCE in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
Drug Interactions with Dalvance
Drug-Laboratory Test Interactions Drug-laboratory test interactions have not been reported.
DALVANCE at therapeutic concentrations does not artificially prolong prothrombin time (PT) or activated partial thromboplastin time (aPTT).
Drug-Drug Interactions No clinical drug-drug interaction studies have been conducted with
DALVANCE. There is minimal potential for drug-drug interactions between DALVANCE and cytochrome P450 (CYP450) substrates, inhibitors, or inducers .
Pregnancy Safety for Dalvance
Pregnancy Risk Summary There are no adequate and well-controlled studies with DALVANCE use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse developmental outcomes. No treatment-related malformations or embryo-fetal toxicity were observed in pregnant rats or rabbits at clinically relevant exposures of dalbavancin. Treatment of pregnant rats with dalbavancin at 3.5 times the human dose on an exposure basis during early embryonic development and from implantation to the end of lactation resulted in delayed fetal maturation and increased fetal loss, respectively . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data No evidence of embryo or fetal toxicity was found in the rat or rabbit at a dose of 15 mg/kg/day (1.2 and 0.7 times the human dose on an exposure basis, respectively). Delayed fetal maturation was observed in the rat at a dose of 45 mg/kg/day (3.5 times the human dose on an exposure basis). In a rat prenatal and postnatal development study, increased embryo lethality and increased offspring deaths during the first week post-partum were observed at a dose of 45 mg/kg/day (3.5 times the human dose on an exposure basis).
Pediatric Use of Dalvance
Pediatric Use The safety and effectiveness of DALVANCE for the treatment of ABSSSI has been established in pediatric patients aged birth to less than 18 years. Use of DALVANCE for this indication is supported by evidence from adequate and well-controlled studies in adults with additional pharmacokinetic and safety data in pediatric patients aged birth to less than 18 years . There is insufficient information to recommend dosage adjustment for pediatric patients with ABSSSI and CLcr less than 30 mL/min/1.73m 2.
Contraindications for Dalvance
is contraindicated in patients with known hypersensitivity to dalbavancin. Known hypersensitivity to dalbavancin
Overdosage Information for Dalvance
Specific information is not available on the treatment of overdose with DALVANCE, as dose-limiting toxicity has not been observed in clinical studies. In Phase 1 studies, healthy volunteers have been administered cumulative doses of up to 4,500 mg over a period of up to 8 weeks (not an approved dosing regimen), with no signs of toxicity or laboratory results of clinical concern. Treatment of overdose with DALVANCE should consist of observation and general supportive measures.
Although no information is available specifically regarding the use of hemodialysis to treat overdose, in a Phase 1 study in patients with renal impairment less than 6% of the recommended dalbavancin dose was removed.
Clinical Studies of Dalvance
Clinical Studies of DALVANCE in Adult Patients with Acute Bacterial Skin and Skin Structure Infections DALVANCE Two-dose Regimen (1, 000 mg Day 1; 500 mg Day 8) Adult patients with ABSSSI were enrolled in two Phase 3, randomized, double-blind, double-dummy clinical trials of similar design (Trial 1 and Trial 2). The Intent-to-Treat (ITT) population included 1,312 randomized patients. Patients were treated for two weeks with either a two-dose regimen of intravenous DALVANCE (1,000 mg followed one week later by 500 mg) or intravenous vancomycin (1,000 mg or 15 mg/kg every 12 hours, with the option to switch to oral linezolid after 3 days). DALVANCE-treated patients with creatinine clearance of less than 30 mL/min received 750 mg followed one week later by 375 mg. Approximately 5% of patients also received a protocol-specified empiric course of treatment with intravenous aztreonam for coverage of Gram-negative pathogens.
The specific infections in these trials included cellulitis (approximately 50% of patients across treatment groups), major abscess (approximately 30%), and wound infection (approximately 20%). The median lesion area at baseline was 341 cm 2. In addition to local signs and symptoms of infection, patients were also required to have at least one systemic sign of disease at baseline, defined as temperature 38°C or higher (approximately 85% of patients), white blood cell count greater than 12,000 cells/mm 3 (approximately 40%), or 10% or more band forms on white blood cell differential (approximately 23%). Across both trials, 59% of patients were from Eastern Europe and 36% of patients were from North America. Approximately 89% of patients were Caucasian and 58% were males. The mean age was 50 years and the mean body mass index was 29.1 kg/m 2. The primary endpoint of these two ABSSSI trials was the clinical response rate where responders were defined as patients who had no increase from baseline in lesion area 48 to 72 hours after initiation of therapy, and had a temperature consistently at or below 37.6°C upon repeated measurement.
Table 5 summarizes overall clinical response rates in these two ABSSSI trials using the pre-specified primary efficacy endpoint in the ITT population. Table 5. Clinical Response Rates in ABSSSI Trials at 48-72 Hours after Initiation of Therapy 1,2 DALVANCE n/N (%) Vancomycin/Linezolid n/N (%) Difference (95% CI) 3 Trial 1 240/288 233/285 1.5 (-4.6, 7.9) Trial 2 285/371 288/368 -1.5 (-7.4, 4.6) 1 There were 7 patients who did not receive treatment and were counted as non-responders: 6 DALVANCE patients (3 in each trial) and one vancomycin/linezolid patient in Trial 2. 2 Patients who died or used non-study antibacterial therapy or had missing measurements were classified as non-responders. 3 The 95% Confidence Interval (CI) is computed using the Miettinen and Nurminen approach, stratified by baseline fever status. A key secondary endpoint in these two ABSSSI trials evaluated the percentage of ITT patients achieving a 20% or greater reduction in lesion area from baseline at 48-72 hours after initiation of therapy.
Table 6 summarizes the findings for this endpoint in these two ABSSSI trials. Table 6. Patients in ABSSSI Trials with Reduction in Lesion Area of 20% or Greater at 48-72 Hours after Initiation of Therapy 1,2 DALVANCE n/N (%) Vancomycin/Linezolid n/N (%) Difference (95% CI) 3 Trial 1 259/288 259/285 -1.0 (-5.7, 4.0) Trial 2 325/371 316/368 1.7 (-3.2, 6.7) 1 There were 7 patients (as described in Table 5) who did not receive treatment and were counted as non-responders. 2 Patients who died or used non-study antibacterial therapy or had missing measurements were classified as non-responders. 3 The 95% CI is computed using the Miettinen and Nurminen approach, stratified by baseline fever status. Another secondary endpoint in these two ABSSSI trials was the clinical success rate assessed at a follow-up visit occurring between Days 26 to 30. Clinical Success at this visit was defined as having a decrease in lesion size (both length and width measurements), a temperature of 37.6°C or lower, and meeting pre-specified criteria for local signs: purulent discharge and drainage absent or mild and improved from baseline, heat/warmth & fluctuance absent, swelling/induration & tenderness to palpation absent or mild.
Table 7 summarizes clinical success rates at a follow-up visit for the ITT and clinically evaluable population in these two ABSSSI trials. Note that there are insufficient historical data to establish the magnitude of drug effect for antibacterial drugs compared with placebo at the follow-up visits. Therefore, comparisons of DALVANCE to vancomycin/linezolid based on clinical success rates at these visits cannot be utilized to establish non-inferiority.
Table 7. Clinical Success Rates in ABSSSI Trials at Follow-Up (Day 26 to 30) 1,2 DALVANCE n/N (%) Vancomycin/Linezolid n/N (%) Difference ( 95% CI) 3 Trial 1 ITT 241/288 (83.7%) 251/285 (88.1%) -4.4% (-10.1, 1.4) CE 212/226 (93.8%) 220/229 (96.1%) -2.3% (-6.6, 2.0) Trial 2 ITT 327/371 (88.1%) 311/368 (84.5%) 3.6% (-1.3, 8.7) CE 283/294 (96.3%) 257/272 (94.5%) 1.8% (-1.8, 5.6) 1 There were 7 patients (as described in Table 5) who did not receive treatment and were counted as failures in the analysis. 2 Patients who died, used non-study antibacterial therapy, or had an unplanned surgical intervention 72 hours after the start of therapy were classified as Clinical Failures. 3 The 95% CI is computed using the Miettinen and Nurminen approach, stratified by baseline fever status. Table 8 shows outcomes in patients with an identified baseline pathogen, using pooled data from Trials 1 and 2 in the microbiological ITT (microITT) population. The outcomes shown in the table are clinical response rates at 48 to 72 hours and clinical success rates at follow-up (Day 26 to 30), as defined above.
Table 8. Outcomes by Baseline Pathogen (Trial 1, 2; MicroITT) 1 Early Clinical Response at 48-72 hours Early Respon der 2 ≥ 20 % reduction in lesion size Clinical Success at Day 26 to 30 Pathogen DALVANCE n/N (% ) Comparator n/N (%) DALVANCE n/N (% ) Comparator n/N (%) DALVANCE n/N (% ) Comparator n/N (%) Staphylococcus aureus Methicillin-susceptible Methicillin-resistant 206/257 134/167 72/90 219/256 163/189 56/67 239/257 156/167 83/90 232/256 173/189 59/67 217/257 142/167 75/90 229/256 171/189 57/67 Streptococcus agalactiae 6/12 11/14 10/12 10/14 10/12 11/14 Streptococcus pyogenes 28/37 24/36 32/37 27/36 33/37 32/36 Streptococcus anginosus group 18/22 23/ 25 21/22 25/25 21/22 23/25 Enterococcus faecalis 8/12 10/13 12/12 12/13 12/12 11/13 All DALVANCE dosing regimens in Trials 1 and 2 consisted of two doses. 1 There were 2 patients in the DALVANCE arm with methicillin-susceptible S. aureus at baseline who did not receive treatment and were counted as non-responders/failures. 2 Early Responders are patients who had no increase from baseline in lesion area 48 to 72 hours after initiation of therapy, and had a temperature consistently at or below 37.6°C upon repeated measurement. DALVANCE 1, 500 mg Single Dose Regimen Adult patients with ABSSSI were enrolled in a Phase 3, double-blind, clinical trial. The ITT population included 698 patients who were randomized to DALVANCE treatment with either a single 1,500 mg dose or a two-dose regimen of 1,000 mg followed one week later by 500 mg (Trial 3). Patients with creatinine clearance less than 30 mL/min had their dose adjusted (Section 2.2 ). Approximately 5% of patients also received a protocol-specified empiric course of treatment with intravenous aztreonam for coverage of Gram-negative pathogens.
The specific infections and other patient characteristics in this trial were similar to those described above for previous ABSSSI trials. The primary endpoint in this ABSSSI trial was the clinical response rate where responders were defined as patients who had at least a 20% decrease from baseline in lesion area 48 to 72 hours after randomization without receiving any rescue antibacterial therapy. The secondary endpoint was the clinical success rate at a follow-up visit occurring between Days 26 and 30, with clinical success defined as having at least a 90% decrease from baseline in lesion size, a temperature of 37.6°C or lower, and meeting pre-specified criteria for local signs: purulent discharge and drainage absent or mild and improved from baseline (for patients with wound infections), heat/warmth and fluctuance absent, swelling/induration and tenderness to palpation absent or mild.
Table 9 summarizes results for these two endpoints in the ITT population. Note that there are insufficient historical data to establish the magnitude of drug effect for antibacterial drugs compared with placebo at the follow-up visit. Therefore, comparisons between treatment groups based on clinical success rates at this visit cannot be utilized to establish non-inferiority.
Table 9. Primary and Secondary Efficacy Results in ABSSSI Patients (Trial 3) 1,2 DALVANCE, n/N (%) Single Dose ( 1, 500 mg ) T wo doses ( 1, 000 mg Day 1/ 500 mg Day 8) Difference (95% CI) 3 Clinical Responders at 48-72 Hours (ITT) 284/349 294/349 -2.9 (-8.5, 2.8) Clinical Success at Day 26-30 (ITT) 295/349 297/349 -0.6 (-6.0, 4.8) Clinical Success at Day 26-30 (CE) 250/271 247/267 -0.3 (-4.9, 4.4) 1 There were 3 patients in the two-dose group who did not receive treatment and were counted as non-responders. 2 Patients who died or used non-study antibacterial therapy or had missing measurements were classified as non-responders. 3 The 95% Confidence Interval (CI) is computed using the Miettinen and Nurminen approach. Abbreviations: ITT-intent to treat; CE-clinically evaluable Table 10 shows outcomes in patients with an identified baseline pathogen from Trial 3 in the microbiological ITT (microITT) population. The outcomes shown in the table are clinical response rates at 48 to 72 hours and clinical success rates at follow-up (Day 26 to 30), as defined above.
Table 10. Outcomes by Baseline Pathogen (Trial 3; MicroITT) Early Clinical Response at 48-72 hours ≥ 20 % reduction in lesion size Clinical Success at Day 26 to 30 Pathogen Single dose (1, 500 mg) n/N (% ) Two doses (1, 000 mg Day 1/ 500 mg Day 8) n/N (%) Single dose (1, 500 mg) n/N (% ) Two doses (1, 000 mg Day 1/ 500 mg Day 8) n/N (%) Staphylococcus aureus Methicillin-susceptible Methicillin-resistant 123/139 92/103 31/36 133/156 89/96 48/61 124/139 93/103 31/36 140/156 86/96 55/61 Streptococcus agalactiae 6/6 4/6 5/6 5/6 Streptococcus anginosus group 31/33 19/19 29/33 17/19 Streptococcus pyogenes 14/14 18/22 13/14 19/22 Enterococcus faecalis 4/4 8/10 4/4 9/10 In Trials 1, 2, and 3, all patients had blood cultures obtained at baseline. A total of 40 ABSSSI patients who received DALVANCE had bacteremia at baseline caused by one or more of the following bacteria: 26 S. aureus (21 MSSA and 5 MRSA), 6 S. agalactiae, 7 S. pyogenes, 2 S. anginosus group, and 1 E. faecalis. In patients who received DALVANCE, a total of 34/40 (85%) were clinical responders at 48-72 hours and 32/40 (80%) were clinical successes at Day 26 to 30. Clinical Study of DALVANCE in Pediatric Patients with Acute Bacterial Skin and Skin Structure Infections The pediatric trial was a multicenter, open-label, randomized, actively controlled trial (NCT02814916, Trial 4) conducted in pediatric patients 3 months of age to less than 18 years with ABSSSI, not known or expected to be caused exclusively by Gram-negative organisms.
Patients were randomized in a 3:3:1 ratio to receive either DALVANCE single-dose regimen, DALVANCE two-dose regimen, or comparator. The comparator regimens included IV vancomycin for methicillin-resistant Gram-positive infections, or IV oxacillin or flucloxacillin for methicillin-susceptible Gram-positive infections. Patients in the comparator arm received IV treatment for a minimum of 72 hours before an optional switch to oral therapy to complete a total of 10-14 days of antibacterial drug therapy.
Additional 5 patients from birth to < 3 months of age were enrolled and assigned to the DALVANCE single-dose regimen. A study population of 191 pediatric patients received study medication (DALVANCE single dose regimen n=83, DALVANCE two-dose regimen n=78, comparator n=30); 62% of the patients were male and 89% were white, and 83% were from Eastern Europe. The pediatric age groups who received DALVANCE were as follows: 12 to < 18 years (n=58), 6 to < 12 years (n=49), 2 to < 6 years (n=35), 3 months to < 2 years (n=14), and birth < 3 months (n=5). Patients had diagnoses of major cutaneous abscess (53%), cellulitis (29%), or surgical site/traumatic wound infection (18%). The predominant pathogen at baseline was Staphylococcus aureus (84%). The primary objective was to evaluate the safety and tolerability of DALVANCE. The trial was not powered for a comparative inferential efficacy analysis.
Efficacy was assessed in the modified intent-to-treat population (n=183) which included all randomized patients who received any dose of study drug and had a diagnosis of ABSSSI caused by Gram-positive organism(s). Patients with ABSSSI only caused by Gram-negative organisms were excluded. The five patients in the age group birth to < 3 months of age were not included in efficacy analyses since they were enrolled with expanded inclusion criteria and only received the single dose DALVANCE regimen. An early clinical response at 48–72 hours was defined as ≥ 20% reduction in lesion size compared to baseline and no receipt of rescue antibacterial therapy.
The proportion of patients with early clinical response, was 97.3% (73/75) in the DALVANCE single-dose arm, 93.6% (73/78) in the DALVANCE two-dose arm, and 86.7% (26/30) in the comparator arm. The difference in responder rates between the dalbavancin single-dose and comparator arms was 10.7%, with an exact 97.5% confidence interval (CI) of (-1.7%, 31.6%). The difference in responder rates between the dalbavancin two-dose and comparator arms was 6.9%, with an exact 97.5% CI of (-6.4%, 27.7%). Clinical cure was defined as resolution of the clinical signs and symptoms of infection, when compared to baseline, and no additional antibacterial treatment for the disease under study. In patients, 3 months of age or older in the mITT population, the clinical cure rate at the test of cure (TOC) visit (28 ± 2 days) was 94.7% (71/75) in the DALVANCE single-dose arm, 92.3% (72/78) in the DALVANCE two-dose arm and 100% (30/30) in the comparator arm.
The difference in cure rates between the dalbavancin single-dose and comparator arms was -5.3%, with an exact 97.5% CI of (-15.1%, 10.5%). The difference in cure rates between the dalbavancin two-dose and comparator arms was -7.7%, with an exact 97.5% CI of (-17.9%, 8.3%).
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
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