AMENDED AND RESTATED CHANGE OF CONTROL AGREEMENT

Exhibit 10.9

AMENDED AND RESTATED

CHANGE OF CONTROL AGREEMENT

THIS AMENDED AND RESTATED CHANGE OF CONTROL AGREEMENT (this “ Agreement ”), is made on this 12th day of December, 2008, by and between VIROPHARMA INCORPORATED (the “ Company ”) and                     (the “ Employee ”).

WHEREAS, the Employee serves as an employee of the Company; and

WHEREAS, the Company and the Employee are parties to that certain Change in Control Agreement (the “Prior Agreement”), pursuant to which the Company and the Employee established certain protections for the Employee in the event of Employee’s termination of employment under the circumstances described herein; and

WHEREAS, the Company and Employee now desire to amend and restate the Prior Agreement in order to ensure that no excise tax will apply to the payments and benefits provided to the Employee pursuant to this Agreement by application of Section 409A of the Internal Revenue Code of 1986, as amended, and its implementing regulations and guidance (“Section 409A”).

NOW, THEREFORE, in consideration of the foregoing and the mutual covenants and promises contained herein, and intending to be bound hereby, the parties agree as follows:

SECTION 1 Definitions . As used herein:

1.1. “ Base Salary ” means, as of any given date, the annual base rate of salary payable to the Employee by the Company, as then in effect; provided, however, that in the case of a resignation by the Employee for the Good Reason described in Section 1.7.3, “Base Salary”

will mean the annual base rate of salary payable to the Employee by the Company, as in effect immediately prior to the reduction giving rise to the Good Reason.

1.2. “ Board ” means the Board of Directors of the Company.

1.3. “ Cause ” means fraud, embezzlement, or any other serious criminal conduct that adversely affects the Company committed intentionally by the Employee in connection with Employee’s employment or the performance of Employee’s duties as an officer or director of the Company or the Employee’s conviction of, or plea of guilty or nolo contendere to, any felony.

1.4. “ Change of Control ” means the happening of an event, which shall be deemed to have occurred upon the earliest to occur of the following events:

1.4.1. the date the stockholders of the Company (or the Board, if stockholder action is not required) approve a plan or other arrangement pursuant to which the Company will be dissolved or liquidated;

1.4.2. the date the stockholders of the Company (or the Board, if stockholder action is not required) approve a definitive agreement to sell or otherwise dispose of all or substantially all of the assets of the Company;

1.4.3. the date the stockholders of the Company (or the Board, if stockholder action is not required) and the stockholders of the other constituent corporations (or their respective boards of directors, if and to the extent that stockholder action is not required) have approved a definitive agreement to merge or consolidate the Company with or into another corporation, other than, in either case, a merger or consolidation of the Company in which holders of shares of the Company’s voting capital stock immediately prior to the merger or consolidation will have more than 50% of the ownership of voting capital stock of the surviving corporation immediately after the merger or consolidation (on a fully diluted basis), which voting capital stock is to be held in the same proportion (on a fully diluted basis) as such holders’ ownership of voting capital stock of the Company immediately before the merger or consolidation;

1.4.4. the date any entity, person or group (within the meaning of Section 13(d)(3) or Section 14(d)(2) of the Exchange Act), other than (i) the Company, or (ii) any of its subsidiaries, or (iii) any employee benefit plan (or related trust) sponsored or maintained by the Company or any of its subsidiaries, or (iv) any affiliate (as such term is defined in Rule 405 promulgated under the Securities Act) of any of the foregoing, shall have acquired beneficial ownership of, or shall have acquired voting control over, 50% or more of the outstanding shares of the Company’s voting capital stock (on a fully diluted basis), unless the transaction pursuant to which such person, entity or group acquired such beneficial ownership or control (i) resulted from the original issuance by the Company of shares of its voting capital stock, (ii) was approved by at least a majority of Directors who were either members of the Board on the date that this Agreement was originally adopted by the Board or members of the Board for at least twelve (12) months before the date of such approval and (iii) does not otherwise constitute a Change of Control pursuant to Section 1.4.3 of this Agreement;

-2-

1.4.5. the date the Board determines (in its sole discretion) that based on then-currently available information, the events described in Section 1.4.4 are reasonably likely to occur; or

1.4.6. the first day after the date of this Agreement when members of the Board (each a “Director”) are elected such that there is a change in the composition of the Board such that a majority of Directors have been members of the Board for less than twelve (12) months, unless the nomination for election of each new Director who was not a Director at the beginning of such twelve (12) month period was approved by a vote of at least sixty percent (60%) of the Directors then still in office who were Directors at the beginning of such period;

provided, however, for purposes of determining the precise date of any Change of Control, an event described above will be deemed to have occurred on the date on which the last condition required for the consummation of that event is fulfilled or otherwise completed.

1.5. “ Code ” means Internal Revenue Code of 1986, as amended.

1.6. “ Disability ” means the Employee’s inability, by reason of any physical or mental impairment, to substantially perform Employee’s regular duties as contemplated by this Agreement, as determined by the Board in its sole discretion (after affording the Employee the opportunity to present Employee’s case), which inability is reasonably contemplated to continue for at least one year from its commencement and at least 90 days from the date of such determination.

1.7. “ Good Reason ” means, without the Employee’s prior written consent, any of the following:

1.7.1. a change in the Employee’s role such that his or her authority, duties or responsibilities are not substantially equivalent to the Employee’s authority, duties or responsibilities in effect immediately prior to such change;

1.7.2. the location of the facility at which Employee is required to perform his or her duties is more than 50 miles from Exton, Pennsylvania, unless such new location does not increase the Employee’s commuting time;

1.7.3. a reduction of five percent (5%) or more in either of the Employee’s Base Salary or the amount of the Employee’s Target Bonus;

1.7.4. the Company’s failure to pay or make available any material payment or benefit due under this Agreement or any other material breach by the Company of this Agreement.

However, the foregoing events or conditions will constitute Good Reason only if (A) such event or condition occurs during the period commencing on the date of a Change of Control and continuing for twelve (12) consecutive months thereafter and (B) the Employee provides the Company with written objection to the event or condition within 60 days following the occurrence thereof, the Company does not reverse or otherwise cure the event or condition

-3-

within 30 days of receiving that written objection and the Employee resigns Employee’s employment within 90 days following the expiration of that cure period.

1.8. “ Release ” means a release substantially identical to the one attached hereto as Exhibit A.

1.9. “ Target Bonus ” means, with respect to any year, the target amount of the annual bonus that would be payable to the Employee with respect to that year, whether under an employment or incentive agreement, under any bonus plan or policy of the Company or otherwise, assuming that all applicable performance goals are met and conditions to the payment of such bonus are satisfied.

SECTION 2 Certain Terminations Following a Change of Control . If the Employee’s employment with the Company ceases within the twelve (12) month period following the date of a Change of Control as a result of a termination by the Company without Cause, a resignation by the Employee for Good Reason or due to Employee’s death or Disability, then subject to Section 3 and Section 4:

2.1 the Company will make a lump sum cash payment to the Employee of all accrued but unpaid compensation through the date of such termination;

2.2 the Company will make a lump sum cash payment to the Employee equal to             % of the Employee’s Base Salary as in effect on such date (without taking into effect any reduction described in Section 1.7.3 above); and

2.3 for a period of                      months commencing from the date of the Employee’s termination of employment, the Company will waive all applicable premiums otherwise due for any group health continuation coverage elected by the Employee or Employee’s spouse or eligible dependents under COBRA (29 U.S.C. §§ 1161-1169) to the extent the Company would have paid such premiums for Employee during Employee’s term of employment with the Company;

provided , however , that if the Company’s obligation to make the payments provided for in clause 2.2 above arises due to the Employee’s death or Disability, the cash payments described in clause 2.2 will be reduced by the amount of benefits paid or payable to the Employee (or Employee’s representative(s), heirs, estate or beneficiaries) pursuant to the life insurance or disability plans, policies or arrangements of the Company by virtue of Employee’s death or Disability (including, for this purpose, only that portion of such life insurance or disability benefits funded by the Company or by premium payments made by the Company). The payments and benefits described in this section are in lieu of (and not in addition to) any other severance plan, fund, agreement or other arrangement maintained by the Company.

SECTION 3 Parachute Payments . Payments under Section 2 shall be made without regard to whether the deductibility of such payments (or any other payments) would be limited or precluded by Section 280G of the Code and without regard to whether such payments would subject Employee to the federal excise tax levied on certain “excess parachute payments” under Section 4999 of the Code; provided, however, that if the Total After-Tax Payments (as defined

-4-

below) would be increased by limitation or elimination of any amount payable under Section 2, then the amount payable under such section will be reduced to the extent necessary to maximize the Total After-Tax Payments. The determination of whether and to what extent such payments are required to be reduced in accordance with the preceding sentence will be made at the Company’s expense by an independent, certified public accounting firm selected by the Board. In the event of any underpayment or overpayment