Efficacy and Safety of Rizatriptan Wafer for the Acute Treatment of Migraine

Rizatriptan is a potent, highly selective 5HT1B/1D agonist with rapid onset of action for acute treatment of migraine. Rizatriptan wafer1 is a novel, freeze-dried dosage formulation of rizatriptan which rapidly disintegrates on the tongue, is swallowed with saliva, and may be taken without liquids. The efficacy and tolerability of rizatriptan wafer were examined in a placebo-controlled, double-blind, outpatient study in 555 migraineurs. The primary efficacy endpoint was pain relief at 2 h. From 30 min onwards, significantly more patients experienced pain relief and became pain-free after rizatriptan 10-mg wafer compared to placebo. At 2 h, the percentage of patients with pain relief was significantly higher after rizatriptan 10-mg wafer (74%), 5-mg wafer (59%) compared with placebo (28%). Rizatriptan 10-mg wafer was superior to rizatriptan 5-mg wafer on pain relief at 1.5 and 2 h ( p<0.05). Significantly more patients were pain-free at 2 h after rizatriptan 10-mg wafer (42%), 5-mg wafer (35%) compared with placebo (10%). Both doses of rizatriptan wafer were well tolerated. Rizatriptan wafer is a convenient, highly effective new formulation for acute treatment of migraine.

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Nasal Delivery of Acute Medications for Migraine: The Upper Versus Lower Nasal Space

Journal of Clinical Medicine ◽

10.3390/jcm10112468 ◽

2021 ◽

Vol 10 (11) ◽

pp. 2468

Author(s):

Vincent Martin ◽

John Hoekman ◽

Sheena K. Aurora ◽

Stephen B. Shrewsbury

Keyword(s):

Acute Treatment ◽

Drug Efficacy ◽

Hepatic Metabolism ◽

Rapid Onset ◽

Systemic Circulation ◽

Nasal Delivery ◽

Attractive Alternative ◽

Gi Tract ◽

Onset Of Action ◽

First Pass

The acute treatment of migraine requires effective drugs that are well tolerated and provide rapid and consistent pain relief. Oral tablets are the most commonly used acute treatment for migraine; however, their effectiveness is limited by the rate of gastrointestinal (GI) tract absorption and first-pass hepatic metabolism, and they may not be ideal for patients experiencing GI motility issues. Nasal delivery is an attractive alternative route as it may circumvent GI tract absorption, avoid first-pass metabolism in the liver, and potentially reduce the frequency of GI adverse events. The large surface area and high vascularity within the nose may permit rapid absorption of therapeutics into the systemic circulation, allowing for rapid onset of action. However, the site of drug deposition (upper versus lower nasal cavity) may influence drug pharmacokinetics. Most approved nasal migraine therapies target the lower nasal space where the epithelium is less permeable, and they may be quickly cleared away due to increased ciliary function or dripping from the nose or swallowing, resulting in variable absorption and limited bioavailability. Together with its abundant vascularization, relative mucosal thickness stability, and low clearance rates, the upper nasal space harnesses the benefits of nasal delivery to potentially maximize drug efficacy.

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Evaluation of Leponex (Clozapine) in Schizophrenia with Acute Symptomatology

Journal of International Medical Research ◽

10.1177/030006057300100707 ◽

1973 ◽

Vol 1 (7) ◽

pp. 627-629 ◽

Cited By ~ 6

Author(s):

K Singer ◽

C M Lam

Keyword(s):

Side Effect ◽

Aggressive Behaviour ◽

Rapid Onset ◽

Onset Of Action ◽

Double Blind ◽

Low Dosage

Thirty-three in-patients, diagnosed as suffering from schizophrenia with acute symptomatology, were involved in a double-blind cross-over trial comparing Leponex (clozapine) with placebo. Leponex was found to be effective, particularly in the control of paranoid manifestations and excited and aggressive behaviour, with rapid onset of action. The drug should however be used with some caution at this stage because of its hypotensive effects, which led to collapse in 13% of cases in the initial stages of treatment. This side-effect could be avoided by starting on low dosage.

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Two replicate randomized, double-blind, placebo-controlled trials of the time to onset of pain relief in the acute treatment of migraine with a fast-disintegrating/rapid-release formulation of sumatriptan tablets

Clinical Therapeutics ◽

10.1016/j.clinthera.2005.04.003 ◽

2005 ◽

Vol 27 (4) ◽

pp. 407-417 ◽

Cited By ~ 38

Author(s):

F SHEFTELL ◽

C DAHLOF ◽

J BRANDES ◽

R AGOSTI ◽

M JONES ◽

...

Keyword(s):

Pain Relief ◽

Acute Treatment ◽

Controlled Trials ◽

Double Blind ◽

Release Formulation ◽

Double Blind Placebo ◽

Rapid Release ◽

Time To Onset

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P.010 Efficacy, safety, and tolerability of ubrogepant for the acute treatment of migraine: a single-attack phase 3 study, ACHIEVE II

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

10.1017/cjn.2019.111 ◽

2019 ◽

Vol 46 (s1) ◽

pp. S16 ◽

Cited By ~ 1

Author(s):

RB Lipton ◽

DW Dodick ◽

J Ailani ◽

K Lu ◽

H Lakkis ◽

...

Keyword(s):

Pain Relief ◽

Acute Treatment ◽

Statistical Significance ◽

Phase 3 ◽

Double Blind ◽

Primary Endpoints ◽

Safety Population ◽

Secondary Endpoints ◽

Attack Phase ◽

Headache Pain

Background: To evaluate efficacy, safety, and tolerability of ubrogepant for acute treatment of migraine attacks. Methods: Multicenter, double-blind, phase 3 study (NCT02867709). Randomized patients (1:1:1, placebo or ubrogepant 25mg or 50mg) had 60 days to treat one migraine attack (moderate/severe pain intensity). Co-primary efficacy endpoints (2 hours post initial dose): headache pain freedom and absence of most bothersome migraine-associated symptom (MBS). Secondary endpoints: pain relief, sustained pain relief, sustained pain freedom, and absence of migraine-associated symptoms. Results: 1686 patients were randomized (safety population: n=1465; mITT population: n=1355). Mean age: 41 years; white: 81%; female: 89%. Significantly greater proportions of ubrogepant- than placebo-treated patients achieved 2-hour pain freedom (placebo: 14.3%; 25mg: 20.7%, adjusted P=0.0285; 50mg: 21.8%, adjusted P=0.0129) and absence of MBS for 50mg (placebo: 27.4%; 50mg: 38.9%, adjusted P=0.0129). Secondary endpoints (except absence of nausea at 2h) met statistical significance versus placebo for ubrogepant 50mg. Absence of MBS and secondary outcomes were not significant for 25mg after multiplicity adjustment. Ubrogepant’s and placebo’s AE profiles were similar. Conclusions: Co-primary endpoints were met for ubrogepant 50mg. Ubrogepant 25mg was significantly superior to placebo for 2h pain freedom. Ubrogepant was well tolerated. Results support the efficacy, tolerability, and safety of ubrogepant for acute treatment of migraine attacks.

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Clinical Evaluation of Etidocaine in Continuous Caudal Analgesia for Pelvic Floor Repair and Post-Operative Pain Relief

Anaesthesia and Intensive Care ◽

10.1177/0310057x7600400312 ◽

1976 ◽

Vol 4 (3) ◽

pp. 239-244 ◽

Cited By ~ 4

Author(s):

L. T. Seow ◽

H. H. Chiu ◽

C. Y. Tye

Keyword(s):

Pelvic Floor ◽

Muscle Relaxation ◽

Rapid Onset ◽

Onset Of Action ◽

Double Blind ◽

Duration Of Action ◽

Pelvic Floor Repair ◽

Post Operative Pain ◽

Caudal Anaesthesia ◽

Caudal Analgesia

A randomized double-blind trial compared 1·0% etidocaine and 1·5% lignocaine (both with 1/200,000 adrenaline), for caudal anaesthesia for pelvic floor repair. Etidocaine was highly effective for the surgical procedure, with rapid onset of action, adequate muscle relaxation and longer duration of action. Its use for post-operative analgesia may be hindered by the concomitant immobilization of the legs. The problem of tachyphylaxis with etidocaine needs further investigation.

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Placebo-Controlled Comparison of Effervescent Acetylsalicylic Acid, Sumatriptan and Ibuprofen in the Treatment of Migraine Attacks

Cephalalgia ◽

10.1111/j.1468-2982.2004.00783.x ◽

2004 ◽

Vol 24 (11) ◽

pp. 947-954 ◽

Cited By ~ 66

Author(s):

The EMSASI ◽

HC Diener ◽

G Bussone ◽

H de Liano ◽

A Eikermann ◽

...

Keyword(s):

Acetylsalicylic Acid ◽

Acute Treatment ◽

Double Blind ◽

Headache Severity ◽

Number Of Patients ◽

Headache Relief ◽

The Difference ◽

Efficacy Criteria ◽

Accompanying Symptoms ◽

New Formulation

Acetylsalicylic acid (ASA) in combination with metoclopramide has been frequently used in clinical trials in the acute treatment of migraine attacks. Recently the efficacy of a new high buffered formulation of 1000 mg effervescent ASA without metoclopramide compared to placebo has been shown. To further confirm the efficacy of this new formulation in comparison with a triptan and a nonsteroidal anti-inflammatory drug (ibuprofen) a three-fold crossover, double-blind, randomized trial with 312 patients was conducted in Germany, Italy and Spain. Effervescent ASA (1000 mg) was compared to encapsulated sumatriptan (50 mg), ibuprofen (400 mg) and placebo. The percentage of patients with reduction in headache severity from moderate or severe to mild or no pain (primary endpoint) was 52.5% for ASA, 60.2% for ibuprofen, 55.8% for sumatriptan and 30.6% for placebo. All active treatments were superior to placebo ( P < 0.0001), whereas active treatments were not statistically different. The number of patients who were pain-free at 2 h was 27.1%, 33.2%, 37.1% and 12.6% for those treated with ASA, ibuprofen, sumatriptan or placebo, respectively. The difference between ASA and sumatriptan was statistically significant ( P = 0.025). With respect to other secondary efficacy criteria and accompanying symptoms no statistically significant differences between ASA and ibuprofen or sumatriptan were found. Drug-related adverse events were reported in 4.1%, 5.7%, 6.6% and 4.5% of patients treated with ASA, ibuprofen sumatriptan or placebo. This study showed that 1000 mg effervescent ASA is as effective as 50 mg sumatriptan and 400 mg ibuprofen in the treatment of migraine attacks regarding headache relief from moderate/severe to mild/no pain at 2 h. Regarding pain-free at 2 h sumatriptan was most effective.

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Rizatriptan Wafer–Sublingual vs. Placebo at the Onset of Acute Migraine

Cephalalgia ◽

10.1046/j.1468-2982.2000.00079.x ◽

2000 ◽

Vol 20 (6) ◽

pp. 585-588 ◽

Cited By ~ 18

Author(s):

JA Klapper ◽

S O’Connor

Keyword(s):

Pain Relief ◽

Oral Administration ◽

Acute Treatment ◽

Placebo Response ◽

Acute Migraine ◽

Double Blind ◽

Double Blind Placebo ◽

Patient Study ◽

Time To Onset

Rizatriptan wafer is a 5HT1B/1D agonist for use in the acute treatment of migraine. It is a freeze-fried formulation, approved for oral administration, which dissolves on the tongue and is swallowed with saliva. In this study the efficacy of sublingually administered rizatriptan 10-mg wafer was evaluated in a randomized, double-blind, placebo-controlled, out-patient study involving 39 migraineurs. Patients were instructed to treat a migraine at the onset of pain in order to evaluate time of onset of pain relief and pain relief at 1 h. The average time to onset of relief was 25 min for patients treated with rizatriptan wafer and 27 min for patients treated with placebo. At 1 h, 50% of the patients receiving rizatriptan wafer and 50% of the patients receiving placebo experienced significant relief. Implications and potential reasons for a high placebo response are discussed.

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Naftifine cream 1% versus clotrimazole cream 1% in the treatment of tinea pedis. Naftifine Podiatric Study Group

Journal of the American Podiatric Medical Association ◽

10.7547/87507315-80-6-314 ◽

1990 ◽

Vol 80 (6) ◽

pp. 314-318 ◽

Cited By ~ 8

Keyword(s):

Randomized Trial ◽

Tinea Pedis ◽

Signs And Symptoms ◽

Rapid Onset ◽

Study Group ◽

Onset Of Action ◽

Double Blind

Fifty-seven subjects with tinea pedis applied naftifine cream 1% or clotrimazole cream 1% to affected areas twice daily for 4 to 6 weeks in a double-blind, randomized trial. Throughout the study, more naftifine-treated than clotrimazole-treated subjects were mycologically cured and globally improved, although differences were not statistically significant. Similar trends favoring naftifine were observed in the resolution of signs and symptoms. Treatment differences noted as early as week 2 suggest that naftifine may have a more rapid onset of action than clotrimazole.

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Onset of analgesia by a topically administered flurbiprofen lozenge: a randomised controlled trial using the double stopwatch method

British Journal of Pain ◽

10.1177/2049463718756152 ◽

2018 ◽

Vol 12 (4) ◽

pp. 208-216 ◽

Cited By ~ 3

Author(s):

Bernard Schachtel ◽

Sue Aspley ◽

Adrian Shephard ◽

Emily Schachtel ◽

Mary Beth Lorton ◽

...

Keyword(s):

Pain Relief ◽

Sore Throat ◽

Median Time ◽

Controlled Trial ◽

Moderate Intensity ◽

Onset Of Action ◽

Serious Adverse Events ◽

Double Blind ◽

Kaplan Meier ◽

Randomised Controlled

Background: The double stopwatch (DSW) method for determining the onset of analgesic activity has been implemented extensively by investigators studying orally administered drugs. Objective: The aim of this randomised, placebo-controlled trial was to use the DSW method to determine the time to onset of analgesia of a single dose of a topically administered non-steroidal anti-inflammatory drug, flurbiprofen 8.75 mg lozenge. Methods: Adults with acute sore throat (n = 122) were examined to confirm the presence of tonsillopharyngitis (Tonsillo-Pharyngitis Assessment) and sore throat pain of at least moderate intensity (≥6 on a 0–10 Sore Throat Scale). Lozenges containing flurbiprofen 8.75 mg or inert ingredients (identically flavoured) were administered under double-blind conditions in the clinic while patients assessed pain and pain relief over 3 hours. Onset of analgesia was determined using the DSW method and reported as the Kaplan–Meier median time to meaningful relief. The median time to first perceived relief was also documented. Results: About 78% of flurbiprofen-treated patients reported meaningful pain relief compared with 48% of placebo-treated patients (p < 0.01); median time to meaningful relief for flurbiprofen-treated patients was 43 minutes (placebo-treated patients were right-censored due to non-responsivity; p = 0.01). Median time to first perceived pain relief was 11 minutes for flurbiprofen-treated patients and 19 minutes for placebo-treated patients (p = 0.03). Flurbiprofen lozenge was well tolerated, with no serious adverse events occurring and no patient discontinuing due to an adverse event. Conclusion: These results indicate that the DSW method can be successfully applied to the evaluation of the onset of action of a locally administered analgesic in patients with acute sore throat, demonstrating that the onset of action (time to meaningful pain relief) of flurbiprofen lozenge was <45 minutes.

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