Excretion of Moxidectin into Breast Milk and Pharmacokinetics in Healthy Lactating Women

ABSTRACTMoxidectin, registered worldwide as a veterinary antiparasitic agent, is currently under development for humans for the treatment of onchocerciasis in collaboration with the World Health Organization. The objective of this study was to assess the pharmacokinetics of moxidectin in healthy lactating women, including the excretion into breast milk. Twelve women, ages 23 to 38 years, weighing 54 to 79 kg, all more than 5 months postpartum, were enrolled, following their plan to wean their infants and provision of informed consent. A single 8-mg, open-label dose was administered orally after consumption of a standard breakfast. Complete milk collection was done for approximately 28 days, and plasma samples were collected for 90 days. Moxidectin concentrations were measured by high-performance liquid chromatography (HPLC) with fluorescence detection, with a validated range of 0.08 to 120 ng/ml. Noncompartmental pharmacokinetic methods were used to find the following results: peak concentration in plasma (Cmax), 87 ± 25 ng/ml; time toCmax(tmax), 4.18 ± 1.59 h; terminal-phase elimination half-life (t1/2), 832 ± 321 h; total area under the concentration-time curve (AUC), 4,046 ± 1,796 ng·h/ml; apparent oral dose clearance (CL/F), 2.35 ± 1.07 l/h; ratio of CL/Fto the terminal-phase disposition rate constant, λz(Vλz/F), 2,526 ± 772 liters; percentage of maternal dose excreted in milk, 0.701 ± 0.299%; absolute amount excreted in milk, 0.056 ± 0.024 mg; relative infant dose, 8.73 ± 3.17% of maternal dose assuming complete absorption; clearance in milk (CLmilk), 0.016 ± 0.009 liter/h. Nine of 12 subjects reported adverse events, all of which were considered treatment emergent but not drug related and were mostly reported during the long outpatient period 8 to 90 days after dose administration. The most frequently reported adverse events were headache and nausea (n= 4), oropharyngeal pain (n= 2), rhinitis, viral pharyngitis, and viral upper respiratory tract infection (n= 2).

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CTIM-03. AUTOLOGOUS ADOPTIVE IMMUNE-CELL THERAPY ELICITED A DURABLE RESPONSE WITH ENHANCED IMMUNE REACTION SIGNATURES IN PATIENTS WITH RECURRENT GLIOBLASTOMA: AN OPEN LABEL, PHASE I/IIA TRIAL

Neuro-Oncology ◽

10.1093/neuonc/noab196.195 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi49-vi49

Author(s):

Jaejoon Lim ◽

Young Joon Park ◽

Ju Won Ahn ◽

Jeong Min Sim ◽

Suwan Kim ◽

...

Keyword(s):

Adverse Events ◽

Cell Therapy ◽

Phase I ◽

Mononuclear Cells ◽

Immune Reaction ◽

Immune Cell ◽

World Health ◽

Open Label ◽

Durable Response ◽

Recurrent Gbm

Abstract Glioblastoma multiforme (GBM) is an aggressive malignancy classified by the World Health Organization as a grade IV glioma. Despite the availability of aggressive standard therapies, most patients experience recurrence, for which there are currently no effective treatments. We aimed to conduct a phase I/IIa clinical trial to investigate the safety and efficacy of adoptive, ex-vivo-expanded, and activated natural killer cells and T lymphocytes from peripheral blood mononuclear cells of patients with recurrent GBM. This study was a single-arm, open-label, investigator-initiated trial on 14 patients recruited between 2013 and 2017. The immune cells were administered via intravenous injection 24 times at 2-week intervals after surgical resection or biopsy. The safety and clinical efficacy of this therapy was examined by assessing adverse events and comparing 2-year overall survival (OS). Transcriptomic analysis of tumor tissues was performed using NanoString to identify the mechanism of therapeutic efficacy. No grade 4 or 5 severe adverse events were observed. The most common treatment-related adverse events were grade 1 or 2 in severity. The most severe adverse event was grade 3 fever. Median OS was 22.5 months, and the median progression-free survival was 10 months. Five patients were alive for over 2 years and showed durable response with enhanced immune reaction transcriptomic signatures without clinical decline until the last follow-up after completion of the therapy. In conclusion, autologous adoptive immune-cell therapy was safe and showed durable response in patients with enhanced immune reaction signatures. This therapy may be effective for recurrent GBM patients with high immune response in their tumor microenvironments. Trial registration: The Korea Clinical Research Information Service database: KCT0003815, Registered 18 April 2019, retrospectively registered.

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P.032 Long-term safety and tolerability of eptinezumab in patients with chronic migraine: A 2-year, open-label, phase 3 trial

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/cjn.2021.314 ◽

2021 ◽

Vol 48 (s3) ◽

pp. S29-S29

Author(s):

D Kudrow ◽

R Cady ◽

B Allan ◽

S Pederson ◽

J Hirman ◽

...

Keyword(s):

Adverse Events ◽

Chronic Migraine ◽

Patient Reported Outcomes ◽

Drug Discontinuation ◽

Upper Respiratory Tract ◽

Open Label ◽

Phase 3 ◽

Patient Reported ◽

Open Label Phase

Background: Eptinezumab is approved in the US for the preventive treatment of migraine and was well tolerated in double-blind, placebo-controlled studies in patients with episodic and chronic migraine (CM). The PREVAIL study evaluated the long-term safety, immunogenicity, and impact on patient-reported outcomes of repeat doses of eptinezumab in patients with CM. Methods: PREVAIL was an open-label, phase 3 trial comprising two 48-week treatment phases. Adults with CM received eptinezumab 300 mg by 30-minute IV every 12 weeks for ≤8 doses, with patients followed up to week 104. Results: 128 adults (mean age, 41.5y) with CM were treated. Over 2 years, the most frequently reported treatment-emergent adverse events were nasopharyngitis (14.1%), upper respiratory tract infection (7.8%), sinusitis (7.8%), influenza (6.3%), bronchitis (5.5%), and migraine (5.5%). Study-drug discontinuation due to adverse events was 6.3%. Anti-eptinezumab antibody incidence peaked at week 24 and declined despite continued dosing, to nondetectable levels at week 104. Patient-reported outcomes were improved at first assessment (week 4) and generally sustained through week 104. Conclusions: In adults with CM, eptinezumab 300 mg demonstrated a favorable safety profile, limited long-term immunogenicity, early and sustained reductions in migraine-related burden, and improvements in health-related quality of life over 2 years.

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Autologous adoptive immune-cell therapy elicited a durable response with enhanced immune reaction signatures in patients with recurrent glioblastoma: An open label, phase I/IIa trial

PLoS ONE ◽

10.1371/journal.pone.0247293 ◽

2021 ◽

Vol 16 (3) ◽

pp. e0247293

Author(s):

Jaejoon Lim ◽

YoungJoon Park ◽

Ju Won Ahn ◽

JeongMin Sim ◽

Su Jung Kang ◽

...

Keyword(s):

Adverse Events ◽

Cell Therapy ◽

Phase I ◽

Mononuclear Cells ◽

Immune Reaction ◽

Immune Cell ◽

World Health ◽

Open Label ◽

Durable Response ◽

Recurrent Gbm

Glioblastoma multiforme (GBM) is an aggressive malignancy classified by the World Health Organization as a grade IV glioma. Despite the availability of aggressive standard therapies, most patients experience recurrence, for which there are currently no effective treatments. We aimed to conduct a phase I/IIa clinical trial to investigate the safety and efficacy of adoptive, ex-vivo-expanded, and activated natural killer cells and T lymphocytes from peripheral blood mononuclear cells of patients with recurrent GBM. This study was a single-arm, open-label, investigator-initiated trial on 14 patients recruited between 2013 and 2017. The immune cells were administered via intravenous injection 24 times at 2-week intervals after surgical resection or biopsy. The safety and clinical efficacy of this therapy was examined by assessing adverse events and comparing 2-year overall survival (OS). Transcriptomic analysis of tumor tissues was performed using NanoString to identify the mechanism of therapeutic efficacy. No grade 4 or 5 severe adverse events were observed. The most common treatment-related adverse events were grade 1 or 2 in severity. The most severe adverse event was grade 3 fever. Median OS was 22.5 months, and the median progression-free survival was 10 months. Five patients were alive for over 2 years and showed durable response with enhanced immune reaction transcriptomic signatures without clinical decline until the last follow-up after completion of the therapy. In conclusion, autologous adoptive immune-cell therapy was safe and showed durable response in patients with enhanced immune reaction signatures. This therapy may be effective for recurrent GBM patients with high immune response in their tumor microenvironments. Trial registration: The Korea Clinical Research Information Service database: KCT0003815, Registered 18 April 2019, retrospectively registered.

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Effect of Fosamprenavir-Ritonavir on the Pharmacokinetics of Dolutegravir in Healthy Subjects

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.03282-14 ◽

2014 ◽

Vol 58 (11) ◽

pp. 6696-6700 ◽

Cited By ~ 7

Author(s):

Ivy Song ◽

Julie Borland ◽

Shuguang Chen ◽

Amanda Peppercorn ◽

Toshihiro Wajima ◽

...

Keyword(s):

Adverse Events ◽

Healthy Subjects ◽

Integrase Inhibitor ◽

Pharmacokinetic Analysis ◽

Hiv Integrase ◽

Open Label ◽

Naive Patient ◽

Time Curve ◽

Once Daily ◽

Treatment Comparison

ABSTRACTDolutegravir (DTG) is an HIV integrase inhibitor (INI) with demonstrated activity in INI-naive and INI-resistant patients. The objective of this open-label, 2-period, single-sequence study was to evaluate the effect of fosamprenavir-ritonavir (FPV-RTV) on the steady-state plasma pharmacokinetics of DTG. Twelve healthy subjects received 50 mg DTG once daily for 5 days (period 1), followed by 10 days of 50 mg DTG once daily in combination with 700/100 mg FPV-RTV every 12 h (period 2). All doses were administered in the fasting state. Serial pharmacokinetic samples for DTG and amprenavir and safety assessments were obtained throughout the study. Noncompartmental pharmacokinetic analysis was performed, and geometric least-squares mean ratios and 90% confidence intervals were generated for within-subject treatment comparison. Fosamprenavir-ritonavir decreased the DTG area under the concentration-time curve, maximum concentration in plasma, and concentration in plasma at the end of the dosing interval by 35%, 24%, and 49%, respectively. Both DTG and DTG with FPV-RTV were well tolerated; no subject withdrew because of adverse events. The most frequently reported drug-related adverse events were rash, abnormal dreams, and nasopharyngitis. The modest decrease in DTG exposure when it was coadministered with FPV-RTV is not considered clinically significant, and DTG dose adjustment is not required with coadministration of FPV-RTV in INI-naive patient populations on the basis of established “no-effect” boundaries of DTG. In the INI-resistant population, as a cautionary measure, alternative combinations that do not include FPV-RTV should be considered. (This study has been registered atClinicalTrials.govunder identifier NCT01209065.)

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Population Pharmacokinetics of Praziquantel in Pregnant and Lactating Filipino Women Infected with Schistosoma japonicum

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00566-20 ◽

2020 ◽

Vol 64 (9) ◽

Author(s):

Amaya L. Bustinduy ◽

Ruwanthi Kolamunnage-Dona ◽

Mark H. Mirochnick ◽

Edmund V. Capparelli ◽

Veronica Tallo ◽

...

Keyword(s):

Body Weight ◽

Breast Milk ◽

Late Gestation ◽

Reproductive Age ◽

World Health ◽

Therapeutic Drug ◽

Postpartum Women ◽

Safety And Efficacy ◽

Lactating Women ◽

Apparent Clearance

ABSTRACT An estimated 40 million women of reproductive age are infected with one of three species of the waterborne parasite Schistosoma spp. Treatment with praziquantel (PZQ) via mass drug administration (MDA) campaigns is the mainstay of schistosomiasis control for populations living in areas of endemicity. The World Health Organization recommends that pregnant and lactating women be included in schistosomiasis MDA programs, and several recent studies have evaluated the safety and efficacy of PZQ use during pregnancy. To date, there are no data describing PZQ pharmacokinetics (PK) during pregnancy or among lactating postpartum women. As part of a randomized controlled trial investigating the safety and efficacy of PZQ during human pregnancy, we examined the PK of this therapeutic drug among three distinct cohorts of women infected with S. japonicum in Leyte, Philippines. Specifically, we studied the PK properties of PZQ among early- and late-gestation pregnant women (n = 15 each) and lactating postpartum women (n = 15) with schistosomiasis. We found that women in early pregnancy had increased apparent clearance and lower area-under-the-curve (AUC0–24) values that may be related to physiological changes in drug clearance and/or changes in oral bioavailability. There was no relationship between body weight and apparent clearance. The mean ± standard deviation partition ratio of plasma to breast milk was 0.36. ± 0.13. The estimated median infant PZQ daily dose would be 0.037 mg/kg of body weight ingested from breast milk, which is significantly lower than the dosage required for antischistosomal activity and not known to be harmful to the infant. Our PK data do not support the suggestion to delay breastfeeding 72 h after taking PZQ. Results can help inform future drug efficacy studies in pregnant and lactating women with schistosomiasis.

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Pharmacokinetics of Dapivirine Transfer into Blood Plasma, Breast Milk, and Cervicovaginal Fluid of Lactating Women Using the Dapivirine Vaginal Ring

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01930-18 ◽

2019 ◽

Vol 63 (3) ◽

Cited By ~ 6

Author(s):

Lisa M. Noguchi ◽

Craig Hoesley ◽

Cliff Kelly ◽

Rachel Scheckter ◽

Katherine Bunge ◽

...

Keyword(s):

Breast Milk ◽

Hiv Infection ◽

Phase 1 ◽

Vaginal Ring ◽

Adult Women ◽

Open Label ◽

Lactating Women ◽

Sexually Transmitted ◽

Hiv Prevention Strategies ◽

Cervicovaginal Fluid

ABSTRACT Breastfeeding (BF) women are an important population for biomedical HIV prevention strategies, but they are rarely included in trials. The 25-mg dapivirine vaginal ring (VR) reduced women’s risk of sexually transmitted HIV infection in two phase 3 trials conducted in Africa. We conducted a phase 1, open-label study (MTN-029/IPM 039) of dapivirine VR use among lactating women in Pittsburgh, PA, and Birmingham, AL, USA. MTN-029/IPM 039 enrolled 16 healthy adult women who had already weaned their infants but were still able to express breast milk. Women were instructed to use the VR continuously for 14 days and provided milk, plasma, and cervicovaginal fluid (CVF) samples for pharmacological analysis. No infants were exposed to the drug, but infant dosage was estimated according to FDA guidance. Adverse events (AEs) were collected at all contacts. The study was completed with 100% participant retention. Median dapivirine concentrations were 676 pg/ml in breast milk, 327 pg/ml in plasma (milk/plasma ratio ∼2.0), and 36.25 ng/mg in CVF. Six participants experienced 10 total AEs, none of which required VR discontinuation. The estimated mean daily infant dosage was 74.3 ng/kg/day. In this first study of dapivirine exposure during lactation, dapivirine VR use was associated with lower concentrations of detectable dapivirine in milk and plasma than in CVF samples and a favorable safety profile. Estimated daily levels of infant dapivirine exposure were also low. Additional studies are needed to evaluate longer periods of dapivirine VR use among BF mother-infant pairs living in regions with higher incidence of sexually transmitted HIV infection. (This study has been registered at ClinicalTrials.gov under registration no. NCT02808949.)

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A single-arm study to evaluate the transfer of drospirenone to breast milk after reaching steady state, following oral administration of 4 mg drospirenone in healthy lactating female volunteers

Women s Health ◽

10.1177/1745506520957192 ◽

2020 ◽

Vol 16 ◽

pp. 174550652095719

Author(s):

Dace Melka ◽

Kalev Kask ◽

Enrico Colli ◽

Pedro-Antonio Regidor

Keyword(s):

Steady State ◽

Breast Milk ◽

Area Under The Curve ◽

Average Concentration ◽

Primary Objective ◽

Repeated Dose ◽

Open Label ◽

Time Curve ◽

Dose Administration ◽

Concentration Time

Objective: The primary objective of this trial was to assess the transfer of drospirenone to breast milk after daily administration of an oral test preparation containing 4 mg of drospirenone at the steady state. The secondary objective of the trial was to assess safety based on clinical and laboratory measurements and reporting of adverse events and/or adverse drug reactions. Patients and Methods: This was an open label, non-comparative single-center study. Drospirenone 4 mg per day was the first postpartum contraceptive for the study participants who were no longer breastfeeding yet were still lactating. It was administered for 7 days to achieve steady-state concentration. All participants were volunteers who planned to use oral contraceptives as their family planning method in the future. Results: Twelve volunteers completed the trial according to the protocol, and the samples of all 12 study completers were analyzed. The average concentration–time curve of drospirenone in plasma 24 h after the administration of the last dose (area under the curve (0–24 h)) was 635.33 ng h/mL and 120 h after the single repeated dose administration (area under the curve (0–120 h)) was 1180.57 ng h/mL, respectively. The average Cmax was 48.64 ng/mL. The average concentration–time curve of drospirenone in milk 24 h after the administration of the last dose (area under the curve (0–24 h)) was 134.35 ng h/mL and 120 h after the single repeated dose administration (area under the curve (0–120 h)) was 227.17 ng h/mL, respectively. The average Cmax was 10.34 ng/mL. Conclusion: On average, 18.13% of plasma drospirenone made it to breast milk and the highest concentration of drospirenone in breast milk was 17.55% of that in plasma. The total quantity of drospirenone passing to breast milk is on average 4478 ng during a 24-h period representing 0.11% of the maternal daily dose. Thus, at the recommended doses, no effects on breastfed newborns/infants are anticipated with drospirenone 4 mg.

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A236 LINACLOTIDE IS NOT DETECTABLE IN BREAST MILK OF LACTATING WOMEN: AN OPEN-LABEL, PHASE 1 STUDY

Journal of the Canadian Association of Gastroenterology ◽

10.1093/jcag/gwab002.234 ◽

2021 ◽

Vol 4 (Supplement_1) ◽

pp. 285-287

Author(s):

N Crittenden ◽

D McGeeney ◽

Y Assouline-Dayan ◽

K Boutros ◽

M Syrzycka ◽

...

Keyword(s):

Breast Milk ◽

Phase 1 ◽

Cumulative Exposure ◽

Human Breast Milk ◽

Open Label ◽

Idiopathic Constipation ◽

Once Daily ◽

Lactating Women ◽

Amino Acid Peptide ◽

Institutional Review

Abstract Background Linaclotide (LIN) is a guanylate cyclase-C agonist approved to treat adults with irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC). As LIN is a 14-amino acid peptide, no absorption from the gastrointestinal tract is expected following oral administration. However, LIN levels in human breast milk have not been determined. Aims To determine the levels of LIN and its active metabolite, MM-419447, excreted in breast milk after multiple once-daily doses of LIN (72 µg, 145 μg, or 290 μg) in lactating women. Methods This was a multicenter, open-label, multidose, Phase 1, milk-only lactation study (NCT02220348) in lactating women aged 18–45 years who were actively breastfeeding or pumping for ≥4 weeks and were already taking LIN 72 μg, 145 μg, or 290 μg therapeutically for IBS-C or CIC. Participants continued their LIN dose once daily for the 3 study days, with breast milk extractions at −1 to 0 hours (pre-dose) on Day 1 and −1 to 0 hours and 0–2, 2–4, 4–8, 8–12, 12–16, and 16–24 hours after dosing on Day 3. The pharmacokinetic endpoints were the cumulative amount of LIN and MM-419447 and the percentage dose of LIN excreted into the breast milk over the dosing interval. Adverse events (AEs) were monitored. The study has institutional review board approval. Results Seven women were enrolled in the study (IBS-C, n=1; CIC, n=6) and received LIN (72 μg, n=5; 145 μg, n=1; and 290 μg, n=1). Mean age was 28 (range: 19–35), mean weight was 70 kg (standard deviation [SD]: 12 kg), and mean body mass index was 26 kg/m2 (SD: 4 kg/m2); the majority were white (n=6). Concentrations of LIN and MM-419447 in breast milk samples were below the quantitation limits (<0.25 ng/mL and <1.00 ng/mL, respectively) at all time points for all participants. Cumulative exposure for each dose was 216 μg (72 μg dose), 435 μg (145 μg dose), and 870 μg (290 μg dose). One treatment-emergent AE was reported (mild rash). Conclusions The data collected in this study provide no evidence that breastfeeding infants receive LIN or MM-419447 through breast milk as their concentrations were below the quantitation limit following multiple once-daily doses of LIN 72 μg, 145 μg, or 290 μg. Funding Agencies This study was sponsored by Allergan plc, Dublin, Ireland (prior to acquisition by AbbVie Inc.). Writing and editorial assistance were provided to the authors by Stephanie J. Rippon, MBio, Jane Beck, MA, and Rebecca Fletcher, BA(Hons), of Complete HealthVizion, Inc., Chicago, IL, USA and funded by Allergan plc (prior to acquisition by AbbVie Inc.).

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Differential Effects of Tipranavir plus Ritonavir on Atorvastatin or Rosuvastatin Pharmacokinetics in Healthy Volunteers

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00449-09 ◽

2009 ◽

Vol 53 (10) ◽

pp. 4385-4392 ◽

Cited By ~ 40

Author(s):

P. A. Pham ◽

C. J. L. la Porte ◽

L. S. Lee ◽

R. van Heeswijk ◽

J. P. Sabo ◽

...

Keyword(s):

Single Dose ◽

Steady State ◽

Adverse Events ◽

Confidence Interval ◽

Geometric Mean ◽

Drug Reactions ◽

Open Label ◽

Time Curve ◽

Concentration Time ◽

Gastrointestinal Intolerance

ABSTRACT To identify pharmacokinetic (PK) drug-drug interactions between tipranavir-ritonavir (TPV/r) and rosuvastatin and atorvastatin, we conducted two prospective, open-label, single-arm, two-period studies. The geometric mean (GM) ratio was 1.37 (90% confidence interval [CI], 1.15 to 1.62) for the area under the concentration-time curve (AUC) for rosuvastatin and 2.23 (90% CI, 1.83 to 2.72) for the maximum concentration of drug in serum (C max) for rosuvastatin with TPV/r at steady state versus alone. The GM ratio was 9.36 (90% CI, 8.02 to 10.94) for the AUC of atorvastatin and 8.61 (90% CI, 7.25 to 10.21) for the C max of atorvastatin with TPV/r at steady state versus alone. Tipranavir PK parameters were not affected by single-dose rosuvastatin or atorvastatin. Mild gastrointestinal intolerance, headache, and mild reversible liver enzyme elevations (grade 1 and 2) were the most commonly reported adverse drug reactions. Based on these interactions, we recommend low initial doses of rosuvastatin (5 mg) and atorvastatin (10 mg), with careful clinical monitoring of rosuvastatin- or atorvastatin-related adverse events when combined with TPV/r.

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Long-Term Safety and Effectiveness of Lisdexamfetamine Dimesylate in Adults With Attention-Deficit/Hyperactivity Disorder

CNS Spectrums ◽

10.1017/s1092852900024056 ◽

2009 ◽

Vol 14 (10) ◽

pp. 573-586 ◽

Cited By ~ 61

Author(s):

Richard Weisler ◽

Joel Young ◽

Greg Mattingly ◽

Joseph Gao ◽

Liza Squires ◽

...

Keyword(s):

Attention Deficit Hyperactivity Disorder ◽

Adverse Events ◽

Attention Deficit ◽

Rating Scale ◽

Upper Respiratory Tract ◽

Open Label ◽

Lisdexamfetamine Dimesylate ◽

Double Blind ◽

Hyperactivity Disorder

ABSTRACTObjective: To evaluate the long-term safety and effectiveness of lisdexamfetamine dimesylate (LDX) in the treatment of adults with attention-deficit/hyperactivity disorder (ADHD).Methods: Following a 4-week, placebo-controlled, double-blind trial, 349 adults with ADHD were enrolled into an open-label, single-arm study for up to 12 months. Treatment was initiated at 30 mg/day and titrated up to 70 mg/day at subsequent visits to achieve optimal effectiveness and tolerability. Safety assessments included adverse events inquiries, vital signs, and electrocardiograms while the primary effectiveness assessment was the ADHD Rating Scale (ADHD-RS) total score.Results: A total of 191 (54.7%) subjects completed the study. The most common treatment-emergent adverse events (TEAEs) were upper respiratory tract infection (21.8%), insomnia (19.5%), headache (17.2%), dry mouth (16.6%), decreased appetite (14.3%), and irritability (11.2%). Most TEAEs were mild to moderate in severity. At endpoint, small but statistically significant increases in pulse and blood pressure were noted. Significant improvements in mean ADHD-RS total scores were observed at week 1 and sustained throughout the study (P<.0001 at all postbaseline visits). At endpoint, the mean improvement from baseline ADHD-RS total score was 24.8 (P<.0001).Conclusions: LDX demonstrated a safety profile consistent with long-acting stimulant use and provided continued effectiveness in adults with ADHD for up to 12 months.

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