8-K

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 8–K

CURRENT REPORT

Pursuant to Section 13 OR 15 (d)

of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): May 12, 2016

Recro Pharma, Inc.

(Exact name of registrant as specified in its charter)

Pennsylvania	001-36329	26-1523233
(State or other jurisdiction of incorporation)	(Commission File Number)	(I.R.S. Employer Identification No.)
490 Lapp Road, Malvern, Pennsylvania		19355
(Address of principal executive offices)		(Zip Code)

Registrant’s telephone number, including area code: (484) 395-2470

Not Applicable

(Former name or former address, if changed since last report.)

Check the appropriate box below if the Form 8–K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

¨ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

¨ Soliciting material pursuant to Rule 14a–12 under the Exchange Act (17 CFR 240.14a–12)

¨ Pre–commencement communications pursuant to Rule 14d–2(b) under the Exchange Act (17 CFR 240.14d–2(b))

¨ Pre–commencement communications pursuant to Rule 13e–4(c) under the Exchange Act (17 CFR 240.13e–4(c))

Item 2.02 Results of Operations and Financial Condition.

On May 12, 2016, Recro Pharma, Inc. (the “Company”) issued a press release announcing its financial results for the first quarter ended March 31, 2016. A copy of the press release is furnished as Exhibit 99.1 to this Current Report on Form 8-K.

Item 7.01 Regulation FD Disclosure.

On May 12, 2016, Recro Pharma, Inc. presented a poster entitled “An Evaluation of the Efficacy and Safety of N1539, a Novel Intravenous Formulation of NanoCrystal Meloxicam, in Subjects with Moderate to Severe Pain Following Hysterectomy” at the 35^th Annual Meeting of the American Pain Society in Austin, Texas. A copy of the poster is attached hereto as Exhibit 99.2 and is incorporated herein by reference.

The information disclosed under Items 2.02 and 7.01, including Exhibits 99.1 and 99.2, is being furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, and shall not be deemed to be incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such filing.

Item 9.01 Financial Statements and Exhibits.

(d) Exhibits

Exhibit No.	Document
99.1	Press release of Recro Pharma, Inc., dated May 12, 2016.
99.2	Poster of Recro Pharma, Inc. entitled “An Evaluation of the Efficacy and Safety of N1539, a Novel Intravenous Formulation of NanoCrystal Meloxicam, in Subjects with Moderate to Severe Pain Following Hysterectomy.”

SIGNATURE

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

Date: May 12, 2016

Recro Pharma, Inc.
By:	/s/ Gerri A. Henwood
Name:	Gerri A. Henwood
Title:	Chief Executive Officer

EXHIBIT INDEX

Exhibit No.	Document
99.1	Press release of Recro Pharma, Inc., dated May 12, 2016.
99.2	Poster of Recro Pharma, Inc. entitled “An Evaluation of the Efficacy and Safety of N1539, a Novel Intravenous Formulation of NanoCrystal Meloxicam, in Subjects with Moderate to Severe Pain Following Hysterectomy.”

EX-99.1

Exhibit 99.1

Recro Pharma Reports First Quarter 2016 Financial Results

Enrollment on track in two pivotal Phase III IV meloxicam trials

One trial expected to report top-line results by end of Q3; Other trial to report top-line results by end of Q4

Manufacturing business continues solid performance

MALVERN, PA, May 12, 2016 – Recro Pharma, Inc. (Nasdaq: REPH), a revenue generating specialty pharmaceutical company focused on products for hospital and ambulatory care settings that is currently developing non-opioid products for the treatment of serious acute pain, today reported financial results for the first quarter ended March 31, 2016.

“During the first quarter of 2016, we advanced our lead program, intravenous (IV) meloxicam into pivotal Phase III clinical development for the treatment of acute postoperative pain – one trial in patients following bunionectomy surgery and one trial in patients following abdominoplasty surgery,” said Gerri Henwood, Recro Pharma’s President and Chief Executive Officer. “We continue to expect top-line data from both Phase III trials by year end 2016, with the first of those trials expected to readout by the end of the third quarter of 2016. If positive, we anticipate that data from these pivotal trials, along with other planned trials, will lead to a New Drug Application (NDA) submission to the U.S. FDA in 2017.”

First Quarter 2016 and Recent Highlights

• Strengthened Management Team with the Appointment of Fred Graff as Chief Commercial Officer. Mr. Graff joined the Company in February 2016 and brings over 20 years of senior commercial leadership and expertise in building high-performance sales organizations and launching new products.

• Presented Meloxicam Clinical Data at American Pain Society 35^th Annual Scientific Meeting. The Company presented a poster which highlighted data from a clinical trial evaluating the efficacy and safety of IV meloxicam (N1539), in subjects with moderate to severe pain following open abdominal hysterectomy. The study results demonstrated that IV meloxicam was effective at treating moderate to severe pain following open abdominal hysterectomy and the study met both co- primary endpoints at all dose levels producing statistically significant differences in SPID24 and TOTPAR24 compared with placebo. In this study, IV meloxicam was also safe and well tolerated.

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• Initiated Pivotal Phase III Trial of IV Meloxicam in Bunionectomy Surgery: In February 2016, Recro announced the commencement of dosing in its pivotal Phase III clinical trial evaluating IV meloxicam for acute postoperative pain in patients following bunionectomy surgery, a representative hard tissue surgery. This multicenter, randomized, double-blind, placebo-controlled trial is expected to enroll approximately 200 patients.

• Initiated Pivotal Phase III Trial of IV Meloxicam in Abdominoplasty Surgery: In January 2016, Recro announced the commencement of dosing in its pivotal Phase III clinical trial evaluating IV meloxicam for acute postoperative pain in patients following “mini” abdominoplasty surgery, a representative soft tissue surgery. This multicenter, randomized, double-blind, placebo-controlled trial is expected to enroll approximately 200 patients.

• Reported Positive Phase II Top-Line Results for IV Meloxicam: In January 2016, Recro reported preliminary results from its Phase II clinical trial evaluating IV meloxicam for the treatment of acute pain following bunionectomy surgery. In this trial, IV meloxicam was well tolerated and both the 30mg and 60mg treatment arms demonstrated statistically significant reductions in pain intensity, as measured by SPID48 (p=0.0007 and p=0.0027, respectively) compared to placebo.

Financial Results

As of March 31, 2016, Recro Pharma had cash and cash equivalents of $14.9 million.

Pursuant to the terms of the Company’s credit agreement with OrbiMed, OrbiMed has the option to require the Company to pay down debt with excess free cash flow generated from the Recro Gainesville contract manufacturing facility. In February 2016, the Company paid approximately $2.6 million to OrbiMed, which was 50% of the free cash flow generated during the fourth quarter of 2015. To date, the Company has paid approximately $19.0 million, or 38%, of the original $50.0 million of senior secured term loan from free cash flow generated during the 2015 fiscal year by Recro Gainesville.

For the quarter ended March 31, 2016, Recro Pharma reported a net loss applicable to common shareholders of $6.5 million, or $0.71 per share, compared to a net loss applicable to common shareholders of $4.1 million, or $0.53 per share, for the comparable period in 2015.

Revenues and COGS for the quarter ended March 31, 2016 were $17.7 million and $10.3 million, respectively. There were no revenues and COGS in the comparable period in 2015. The increases in revenues and COGS were the result of the acquired manufacturing business, Recro Gainesville, from Alkermes on April 10, 2015.

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Research and development expenses for the quarter ended March 31, 2016 were $7.8 million, compared to $1.8 million for the same period in 2015. General and administrative expenses for the quarter ended March 31, 2016, were $2.7 million, compared to $2.4 million for the same period in 2015. The increase in research and development expenses were primarily due to the Company’s injectable meloxicam clinical expenses and research and development costs incurred at the Recro Gainesville facility. The increase in general and administrative expenses was primarily due to an increase in management’s salaries, benefits and stock compensation as a result of additional headcount and costs associated with being a public company.

Amortization of intangibles for the quarter ended March 31, 2016, was $0.7 million. There was no amortization of intangibles for the comparable period in 2015.

Interest expense for the quarter ended March 31, 2016, was $1.5 million and consists of interest incurred on our OrbiMed senior secured term loan and amortization of related financing costs. There was no interest expense for the same period in 2015.

About Recro Pharma, Inc.

Recro Pharma is a revenue generating specialty pharmaceutical company focused on products for hospital and ambulatory care settings that is currently developing non-opioid products for the treatment of serious acute pain. Recro Pharma is currently developing IV meloxicam, a proprietary, long-acting preferential COX-2 inhibitor for treatment of acute postoperative pain, and Dex-IN, a proprietary intranasal formulation of dexmedetomidine, for the treatment of peri-procedural pain. Both compounds have successfully completed Phase II clinical trials. As Recro Pharma’s product candidates are not in the opioid class of drugs, the Company believes its candidates would avoid many of the side effects associated with commonly prescribed opioid therapeutics, such as addiction, constipation and respiratory distress, while maintaining analgesic effect.

Recro Pharma also owns and operates a 97,000 square foot, DEA-licensed facility that manufactures five commercial products and receives manufacturing revenues and royalties associated with the sales of these products.

Cautionary Statement Regarding Forward Looking Statements

This press release contains forward-looking statements that involve risks and uncertainties. Such forward looking statements reflect Recro Pharma’s expectations about its future performance and opportunities that involve substantial risks and uncertainties. When used herein, the words “anticipate,” “believe,” “estimate,” “upcoming,” “plan,” “target”, “intend” and “expect” and similar expressions, as they relate to Recro Pharma or its management, are intended to identify such forward-looking statements. These forward looking statements are based on information available to

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Recro Pharma as of the date of this press release and are subject to a number of risks, uncertainties, and other factors that could cause Recro Pharma’s performance to differ materially from those expressed in, or implied by, these forward looking statements. Recro Pharma assumes no obligation to update any such forward-looking statements. Factors that could cause Recro Pharma’s actual performance to materially differ from those expressed in the forward-looking statements set forth in this press release include, without limitation: results and timing of the clinical trials of injectable meloxicam and Dex-IN; the ability to obtain and maintain regulatory approval of injectable meloxicam and Dex-IN, and the labeling under any such approval; regulatory developments in the United States and foreign countries; the Company’s ability to raise future financing for continued development; the Company’s ability to pay its debt; the performance of third-party suppliers and manufacturers; the Company’s ability to obtain, maintain and successfully enforce adequate patent and other intellectual property protection; and the successful commercialization of injectable meloxicam and Dex-IN. In addition, the forward looking statements in this press release should be considered together with the risks and uncertainties that may affect Recro Pharma’s business and future results included in Recro Pharma’s filings with the Securities and Exchange Commission at www.sec.gov. Recro Pharma assumes no obligation to update any such forward looking statements.

CONTACT:

Argot Partners

Susan Kim

(212) 600-1902

susan@argotpartners.com

4

RECRO PHARMA, INC. AND SUBSIDIARIES

Consolidated Balance Sheets

(unaudited)

(amounts in thousands, except share and per share data)

	March 31, 2016			December 31, 2015
Assets
Current assets:
Cash and cash equivalents	$	14,917		$	19,779
Accounts receivable		12,182			8,580
Other recievables		23			36
Inventory		7,638			8,982
Prepaid expenses		934			757
Deferred equity costs		512			542
Total current assets	$	36,206		$	38,676
Property, plant and equipment, net		36,995			37,922
Deferred income taxes		16,043			15,637
Intangible assets,net		39,370			40,016
Goodwill		6,446			6,446
Total assets	$	135,060		$	138,697
Liabilities and Shareholders’ Equity
Current liabilities:
Accounts payable		1,990			1,553
Accrued expenses		5,606			3,418
Current portion of long-term debt		4,859			4,516
Total current liabilities		12,455			9,487
Long-term debt		22,563			25,244
Warrants		2,176			3,770
Contingent consideration		62,824			59,846
Total liabilities		100,018			98,347
Shareholders’ equity:
Preferred stock, $0.01 par value. Authorized, 10,000,000 shares; none issued and outstanding.		—			—
Common stock, $0.01 par value. Authorized, 50,000,000 shares, issued and outstanding, 9,318,255 shares at March 31, 2016 and 9,224,315 shares at December 31, 2015		93			92
Additional paid in-capital		72,551			71,321
Accumulated deficit		(37,602	)		(31,063	)
Total shareholders’ equity		35,042			40,350
Total liabilities and shareholders’ equity	$	135,060		$	138,697

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RECRO PHARMA, INC. AND SUBSIDIARIES

Consolidated Statements of Operations

(unaudited)

(amounts in thousands, except share and per share data)

	Three Months Ended
	March 31,
	2016			2015
Revenue:
Manufacturing, royalty and profit sharing revenue	$	17,138		$	—
Research and development revenue		604			—
Total revenue		17,742			—
Operating expenses:
Cost of sales (excluding amortization of intangible assets)		10,271			—
Research and development		7,808			1,754
General and administrative		2,658			2,386
Amortization of intangible assets		646			—
Change in warrant valuation		(1,594	)		—
Change in contingent consideration valuation		2,978			—
Total operating expenses		22,767			4,140
Operating loss		(5,025	)		(4,140	)
Other income (expense):
Interest income		9			4
Interest expense		(1,512	)		—
Net loss before income taxes		(6,528	)		(4,136	)
Income tax expense		(11	)
Net loss applicable to common shareholders		(6,539	)		(4,136	)
Basic and diluted net loss per common share	$	(0.71	)	$	(0.53	)
Weighted average basic and diluted common shares outstanding		9,251,948			7,768,693

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EX-99.2

Exhibit 99.2

An Evaluation of the Efficacy and Safety of N1539, a Novel Intravenous Formulation of NanoCrystal Meloxicam, in Subjects with Moderate to Severe Pain Following Hysterectomy
Randall J. Mack1, Wei Du, Ph.D2, Alex Freyer, Pharm.D1 1Recro Pharma, Inc., Malvern, PA, USA; 2Clinical Statistics Consulting, Blue Bell, PA, USA INTRODUCTION
N1539 is a novel intravenous (IV) formulation of meloxicam being developed for the management of moderate to severe acute pain. Meloxicam is a nonsteroidal anti-inflammatory drug (NSAID) of the enolic acid class that possesses anti-inflammatory, analgesic, and antipyretic activities, which are believed to be related to the inhibition of cyclooxygenase (COX) and subsequent reduction in prostaglandin biosynthesis (Mobic 2012; Turck 1997; Del Tacca 2002). Oral meloxicam has a slow onset of action, largely due to poor solubility, and is not currently approved for the treatment of acute pain. Absorption is prolonged; the time to maximum observed plasma concentration is approximately 5-6 hours following oral administration (Degner 1997; Turck 1997), which is consistent with its poor aqueous solubility. By increasing the dissolution rate of the active meloxicam moiety, the use of N1539 has been shown to provide a rapid onset of action of meloxicam, thus rendering it suitable for the treatment of acute pain via the IV route.
OBJECTIVE
The primary objective of this study was to determine the analgesic efficacy, duration of effect, and safety of single doses of N1539 in subjects undergoing open abdominal hysterectomy.
METHODS
Subjects All subjects provided informed consent prior to completing any study activities. Selected inclusion criteria:
Females aged 18 to 65 years.
Underwent open abdominal hysterectomy, with an anticipated length of incision to be = 3 inches.
Moderate to severe pain within 6 hours of last morphine dose, with a visual analog scale (VAS) score =45 mm (0 to 100 mm scale).
Selected exclusion criteria:
Active gastrointestinal (GI) bleeding, or any history of peptic ulcer disease.
Known bleeding disorder or was taking agents affecting coagulation.
Underwent any prior abdominal surgical procedure with the exception of inguinal hernia repair or appendectomy by the lateral approach or cesarean section if the surgery was performed more than 1 year prior to study participation and the subject experienced no postoperative complications.
Taking or had taken an opioid chronically (more than 30 consecutive days of daily use) for pain in the past 2 years.
Study Design Two-part, Multi-center Study: Part 1: randomized, single-dose, double-blind, placebo-and active-controlled; Part 2: Multiple-dose, open-label (Part 2 presented separately). Each subject’s study participation consisted of a screening visit, surgery and inpatient evaluation period of variable length, and a follow-up visit 14 days after hospital discharge.
On Postoperative Day 1, subjects were eligible to receive a single study dose within 6 hours following discontinuation of other analgesics. Subjects were followed for 24 hours. Endpoints
Co-Primary Endpoint: Summed pain intensity (PI) difference over the first 24 hours post-dose (SPID24).
Sum of the time-weighted pain relief scores over the first 24 hours post-dose (TOTPAR24). Secondary Endpoints included:
Pain intensity difference (PID) calculated as change from baseline.
Time to first use of rescue analgesia. Patient reported Global Evaluation Scale
Statistical Analysis An analysis of covariance (ANCOVA) model, with treatment as a factor and baseline PI as a covariate, was used to analyze SPID24 and TOTPAR24 to assess the treatment effect. The same ANCOVA model was used for analysis of various secondary endpoints. The Kaplan-Meier method was used to estimate the survival analyses. The PID was calculated by subtracting the baseline PI score from the post-dose PI score. The weight given to each PID score was equal to the elapsed time since the previous evaluation. Subjects who received rescue medication prior to 24 hours had their PI scores recorded immediately prior to rescue and carried forward through 24 hours.
RESULTS Demographics A total of 486 subjects were randomized and treated in this study. However, 26 subjects (all from one study center) were excluded from the efficacy analyses due to potential bias introduced by unblinded personnel performing blinded assessments during the double-blind phase. Therefore, the efficacy population only included 460 treated subjects.
Table 1: Summary of Demographics and Disposition N1539
Placebo Morphine 5 mg 7.5 mg 15 mg 30 mg 60 mg Total Population (n) 64 62 60 91 60 60 89 Age (years) Mean (SD) 47.9 (6.46) 48.0 (7.43) 47.7 (6.27) 47.9 (5.67) 46.9 (6.28) 47.4 (7.40) 47.6 (7.12) Range (32, 65) (28, 63) (29, 62) (36, 63) (31, 65) (25, 62) (29, 63) BMI (kg/m2) Mean (SD) 25.79 (3.654) 26.45 (3.139) 25.17 (3.047) 26.02 (3.250) 25.09 (2.865) 25.61 (3.462) 26.50 (3.266) Range (19.3, 31.6) (18.8, 31.3) (19.9, 31.3) (19.2, 31.2) (19.7, 31.0) (18.8, 31.2) (18.8, 31.5) Race (%) White/ Caucasian 100 100 100 100 100 100 98.9 Gender: Female (%) 100 100 100 100 100 100 100 Baseline Pain Score Mean (SD) 57.8 (7.49) 57.7 (9.59) 61.1 (11.19) 60.5 (11.10) 60.0 (10.13) 59.4 (10.04) 59.5 (9.68) Efficacy Population (n) 60 60 60 80 60 60 80
Efficacy SPID24 (Co-Primary Endpoint)
Overall, there was a statistically significant difference among the groups. Statistically significant differences for SPID24 effect size were seen for each of the N1539 dose groups compared with to placebo (P <0.001).
The SPID24 effect size for N1539 60 mg, 30 mg, and 15 mg dose groups were statistically significantly better than the morphine group (P=0.002). Table 2: SPID24 – LS Mean (SE) Placebo Morphine N1539 5 mg N1539 7.5 mg N1539 15 mg N1539 30 mg N1539 60 mg (N=64) (N=62) (N=60) (N=91) (N=60) (N=60) (N=89)
-4555.9 29615.8 33517.1 34241.3 47176.1 56276.8 54074.4 (3807.05) (3869.24)* (3930.09)* (3189.34)* (3926.20) # (3926.46) # (3225.48)# * p=0.001 vs. placebo # p=0.001 vs. placebo AND p=0.05 vs. morphine Figure 1: SPID24 – Effect Size
2.5 2 CI 1.5 Favors 95% Treatment (Effect Size >0) and 1 size Effect
0.5 0 Morphine N1539 5 mg N1539 7.5 mg N1539 15 mg N1539 30 mg N1539 60 mg Favors
Placebo (Effect Size <0) -0.5 TOTPAR24 (Co-Primary Endpoint)
Overall, there was a statistically significant difference among the groups.
Statistically significant differences for TOTPAR24 effect size were seen for all N1539 dose groups compared to placebo (P<0.001).
The TOTPAR24 effect size for N1539 60 mg, 30 mg, and 15 mg dose groups were statistically significantly better than the morphine group (P<0.001). Table 3: TOTPAR24 – LS Mean (SE)
Placebo Morphine N1539 5 mg N1539 7.5 mg N1539 15 mg N1539 30 mg N1539 60 mg (N=64) (N=62) (N=60) (N=91) (N=60) (N=60) (N=89) 1100.6 2723.3 3124.9 3104.5 3734.3 4130.4 4101.7 (185.36) (188.39)* (191.35)* (155.28)* (191.16) # (191.17) # (157.04) #
* p=0.001 vs. placebo # p=0.001 vs. placebo AND p=0.05 vs. morphine Figure 2: TOTPAR24 – Effect Size
2.5 2 1.5 CI 95% Favors and 1 Treatment size (Effect Size >0)
Effect 0.5 0 Morphine N1539 5 mg N1539 7.5 mg N1539 15 mg N1539 30 mg N1539 60 mg
Favors Placebo (Effect Size <0)
-0.5 Global Evaluation Score (GES) at Hour 24 GES was evaluated at the end of the 24-hour double-blind phase; subjects rated their study treatment as: 0=poor, 1=fair, 2=good, 3=very good, 4=excellent.
There was a statistically significant difference among all active treatment groups compared with placebo, and for N1539 7.5 mg, 15 mg, 30 mg, and 60 mg compared with Morphine
Results demonstrated that subjects treated with N1539 at 7.5 mg or greater were more satisfied with their treatment compared with morphine or placebo.
Figure 3: GES at Hour 24
3.5
#
3 #
24
Hour #
2.5 at # Score *
*
Evaluation 2 Global 1.5 SE) (+/ - 1 Mean
0.5
0
Placebo Morphine 5 mg 7.5 mg 15 mg 30 mg 60 mg
* p=0.001 vs. placebo
# p=0.001 vs. placebo AND p0.01 vs. morphine
Time to First Rescue Medication
Rescue use: placebo (95.0%), morphine (76.7%), N1539 5 mg (60.0%), N1539 7.5 mg (62.5%) N1539 15 mg (45.0%), N1539 30 mg (36.7%), N1539 60 mg (38.8%). In a log-rank analysis, the difference between each active treatment and placebo was statistically significant (P <0.001).
Median time to rescue medication: placebo (1.0 hour), morphine (6.6 hours), N1539 5 mg (12.2 hours), 7.5mg (8.3 hours), N1539 15 mg (18.3 hours), N1539 30 mg (21.9 hours), N1539 60 mg (20.6 hours). In a Cox model, the difference between each active treatment and placebo was statistically significant (P <0.001).
Figure 4: Survival Analysis of Time to First Rescue Medication
100%
80%
Analgesia
Rescue 60% First with Subjects 40% %
20%
0%
0 120 240 360 480 600 720 840 960 1080 1200 1320 1440
Time (Minutes) from First Dose
Placebo Morphine N1539 5 mg N1539 7.5 mg N1539 15 mg N1539 30 mg N1539 60 mg
Pain Intensity Differences at Each Time Point
Statistically significant PID from baseline were detected as early as 10 minutes post-dose and continued throughout the 24-hour double-blind phase in all active treatment groups.
Figure 5: Pain Intensity Differences Over Time
20
0
SE) - (+/ Differences Intensity -20 Pain Mean
-40
-60
0 2 4 6 8 10 12 14 16 18 20 22 24
Time (hr) Since First Dose
Placebo Morphine N1539 5 mg N1539 7.5 mg N1539 15 mg N1539 30 mg N1539 60 mg
Figure 6: Pain Intensity Differences Over Time – Hour 0-2
20
0
SE) - (+/ Differences Intensity -20 Pain Mean
-40
-60
0 20 40 60 80 100 120
Time (minutes) Since First Dose
Placebo Morphine N1539 5 mg N1539 7.5 mg N1539 15 mg N1539 30 mg N1539 60 mg
Safety
Doses up to 60 mg of N1539 were generally well tolerated during the double-blind and open-label periods.
Adverse events were generally reported as mild with no meaningful differences among N1539 treatment groups.
The AE profile observed in the open-label period was generally similar to that seen in the double-blind period.
Five SAEs were reported in the study, none were considered related to study treatment.
One subject discontinued the study due to an AE attributed to the use of morphine as a rescue edication.
Table 4: Summary of Adverse Events – Percent of Subjects
N1539
Placebo Morphine 5 mg 7.5 mg 15 mg 30 mg 60 mg n=64 n=62 n=60 n=91 n=60 n=60 n=89 Anemia 3.1 4.8 3.3 13.2 3.3 1.7 10.1 Anemia Postoperative - 1.6 - - - 3.3 - Constipation - 4.8 5.0 1.1 1.7 - - Flatulence - 4.8 1.7 1.1 3.3 - - Hypokalaemia - 3.2 1.7 1.1 - 1.7 - Insomnia 4.7 8.1 10.0 4.4 5.0 5.0 4.5 Ketonuria 7.8 9.7 6.7 9.9 15 10 10.1 Leukocytosis - - 1.7 - - 3.3 - Pyrexia 1.6 3.2 3.3 2.2 - - - Sinus Tachycardia - - 3.3 - - - 1.1
Anemia
The incidence of anemia was reported across treatment groups with no apparent relation to study dose.
Predetermined criteria for AEs of anemia were: postoperative hemoglobin < 8.0 g/dL OR postoperative hemoglobin between 8.0 - 9.9 g/dL with a decrease of = 0.5 g/dL from screening (within 7 days prior to surgery, no immediate pre-operative laboratory assessments were collected)
Additional review determined that none of the shifts in hemoglobin, for any treatment group, were clinically meaningful
Figure 7: Hemoglobin Shift Plots
Ketonuria
The study reported an unexpected incidence of ketonuria events across all treatment groups.
Subsequent review identified that all AEs of ketonuria were reported at a single study center; this anomaly of ketonuria occurring only at one study may be related to specific differences in the timing of resumption of adequate oral caloric intake and or the use of glucose containing electrolytes, as the degree of ketonuria which occurs in the normal person with a subcaloric intake may reach up to 15 gm per day after complete starvation.
Table 5: Summary of Ketonuria Incidence
N1539
Placebo Morphine 5 mg 7.5 mg 15 mg 30 mg 60 mg All Sites 5 / 64 (7.8) 7 / 62 (9.7) 4 / 60 (6.7) 9 / 91 (9.9) 10 / 60 (15) 6 / 60 (10) 9 / 89 (10.1) Site 27 (Poland) 5 / 7 (71.4) 7 / 8 (87.5) 4 / 5 (80.0) 9 / 10 (90.0) 10 / 10 (100) 6 / 7 (85.7) 9 / 10 (90.0) All except Site 27 0 / 57 (0) 0 / 54 (0) 0 / 55 (0) 0 / 81 (0) 0 / 50 (0) 0 / 53 (0) 0 / 79 (0)
CONCLUSIONS
N1539, at doses of 5 mg to 60 mg, met both Co-Primary Endpoints by producing statistically significant differences in SPID24 and TOTPAR24 compared with placebo.
N1539 also produced statistically significantly better responses in a number of secondary efficacy endpoints compared with placebo.
Dosing with N1539 was safe and well tolerated with a low incidence of AEs, SAEs, and discontinuations due to AE, and no deaths.
REFERENCES
Degner F, Turck D, Pairet M. Pharmacological, pharmacokinetic and clinical profile of meloxicam. Drugs of Today. 1997;33:739-758.
Del Tacca M, Colucci R, Fornai M, Blandizzi C. Efficacy and tolerability of meloxicam, a COX-2 preferential nonsteroidal anti-inflammatory drug. Clin Drug Invest. 2002;22(12):799-818.
Mobic [package insert] Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc; 2012.
Turck D, Busch U, Heinzel G, Narjes H. Clinical pharmacokinetics of meloxicam. Arzneim-Forsch/Drug Res. 1997;47(1):253-258.
Research originally funded by Elan Drug Delivery, Inc. N1539 was subsequently acquired by Recro Pharma, Inc.
Presented at the American Pain Society Annual Scientific Meeting; May 11-14, 2016. Poster # 409